Article. Does Donepezil Treatment Slow the Progression of Hippocampal Atrophy in Patients With Alzheimer s Disease?
|
|
- Prudence Bridges
- 6 years ago
- Views:
Transcription
1 Article Does Donepezil Treatment Slow the Progression of Hippocampal Atrophy in Patients With Alzheimer s Disease? Mamoru Hashimoto, M.D., Ph.D. Hiroaki Kazui, M.D., Ph.D. Keiji Matsumoto, M.D. Yoko Nakano, M.D., Ph.D. Minoru Yasuda, M.D., Ph.D. Etsuro Mori, M.D., Ph.D. Objective: The only approved pharmacological approach for the symptomatic treatment of Alzheimer s disease in Japan is the use of a cholinesterase inhibitor, donepezil hydrochloride. Recent in vivo and in vitro studies raise the possibility that cholinesterase inhibitors can slow the progression of Alzheimer s disease. The purpose of the present study was to determine whether donepezil has a neuroprotective effect in Alzheimer s disease by using the rate of hippocampal atrophy as a surrogate marker of disease progression. Method: In a prospective cohort study, 54 patients with Alzheimer s disease who received donepezil treatment and 93 control patients with Alzheimer s disease who never received anti-alzheimer drugs underwent magnetic resonance imaging (MRI) twice at a 1-year interval. The annual rate of hippocampal atrophy of each subject was determined by using an MRIbased volumetric technique. Background characteristics, age, sex, disease duration, education, MRI interval, apolipoprotein E (APOE) genotype, and baseline Alzheimer s Disease Assessment Scale score were comparable between the treated and control groups. Results: The mean annual rate of hippocampal volume loss among the treated patients (mean=3.82%, SD=2.84%) was significantly smaller than that among the control patients (mean=5.04%, SD=2.54%). Upon analysis of covariance, where those confounding variables (age, sex, disease duration, education, MRI interval, APOE genotype, and baseline Alzheimer s Disease Assessment Scale score) were entered into the model as covariates, the effect of donepezil treatment on hippocampal atrophy remained significant. Conclusions: Donepezil treatment slows the progression of hippocampal atrophy, suggesting a neuroprotective effect of donepezil in Alzheimer s disease. (Am J Psychiatry 2005; 162: ) At present, the only approved pharmacological approach for the symptomatic treatment of Alzheimer s disease in Japan is the use of cholinesterase inhibitors. Donepezil hydrochloride has been demonstrated to have significant effects in slowing symptomatic progression in 24-week placebo-controlled trials (1), and some long-term studies have shown that there is no less benefit after 1 year of treatment (2, 3). One observational study (4) showed that cholinesterase inhibitor treatment alters the natural history of Alzheimer s disease, as indicated by the delay in admission to nursing homes. Furthermore, a longitudinal neuroimaging study using single photon emission computed tomography (SPECT) demonstrated that treatment of patients with Alzheimer s disease with donepezil for 1 year reduced the decline in regional cerebral blood flow (rcbf) (5), suggesting the preservation of functional brain activity in donepezil-treated patients. Although these studies appear to have demonstrated the efficacy of donepezil in slowing down clinical disease progression, it is not clear whether donepezil treatment slows disease progression in Alzheimer s disease. Neuropathologically, Alzheimer s disease is characterized by the presence of neurofibrillary tangles and senile plaques, impaired synaptic function, and cell loss (6). Although these histological features cannot be examined noninvasively, the cell loss that accompanies them can be seen in vivo as atrophy with magnetic resonance imaging (MRI). Among the characteristic neuropathological changes in Alzheimer s disease, the most prominent structural changes at the initial stage occur in the hippocampal formation (7, 8). MRI-based volumetry of the medial temporal lobe structures has been proposed as a useful tool for the clinical diagnosis of Alzheimer s disease (8). Serial MRI studies permit calculation of rates of atrophy over time. It has been proposed that measurement of the rate of atrophy could be used to monitor the effectiveness of antidementia drugs for Alzheimer s disease (9, 10). If an anti-alzheimer drug can slow down the anatomic progression of Alzheimer s disease pathology, this should be detectable as a decrease in the rate of hippocampal atrophy in treated patients
2 HASHIMOTO, KAZUI, MATSUMOTO, ET AL. The purpose of the present study was to determine whether a cholinesterase inhibitor, donepezil hydrochloride, has a neuroprotective effect on Alzheimer s disease. Using an MRI-based volumetric technique, we examined the rates of hippocampal atrophy in donepezil-treated Alzheimer s disease patients and compared the results with those in control patients. Method Subjects and Study Design In the present study, a prospective cohort was compared with a historical control cohort. All procedures followed the clinical study guidelines of the ethics committee of Hyogo Institute for Aging Brain and Cognitive Disorders, a research-oriented hospital, and were approved by the institutional review board. Written informed consent was obtained from the patients or their families. The control group was selected among those who participated in the annual follow-up program before donepezil was introduced. Patients with Alzheimer s disease who were examined at the Hyogo Institute for Aging Brain and Cognitive Disorders were invited to the Hyogo Institute s Alzheimer s disease annual followup program starting in July The consent and availability of a reliable caregiver and the absence of severe behavioral problems impelling institutionalization were the requirements for participating in the program. At baseline, the patients were examined comprehensively by both neurologists and psychiatrists under a short-term admission to the infirmary and were given routine laboratory tests, EEGs, and standardized neuropsychological examinations. The patients medical history was systematically collected from reliable family members by using a database format. Other imaging studies, such as MRIs of the brain, magnetic resonance angiograms of the head and neck, and cerebral perfusion or metabolism studies with positron emission tomography or SPECT were performed at baseline. Neuropsychological tests and MRIs were repeated at 1-year intervals. The clinical and investigative data collected prospectively in a standardized fashion were all added to the database (11). After donepezil hydrochloride was licensed and marketed in November 1999 in Japan, the annual follow-up program was revised to the donepezil follow-up program because most patients with Alzheimer s disease were treated with donepezil. The treated group consisted of consecutive patients with mild to moderate Alzheimer s disease who received donepezil treatment and were enrolled in a prospective longitudinal cohort study between November 1999 and June Treatment with donepezil was a prerequisite for participating in the revised program. After the same baseline assessments as the annual follow-up program were evaluated, the patients received 3 mg/day of donepezil for 1 or 2 weeks and then 5 mg/day (the approved maximum dose in Japan). Donepezil hydrochloride was prescribed for the entire year after the initial MRI, and compliance was monitored at every visit (every 3 months). Neuropsychological tests and MRIs were repeated at 1- year intervals. The treated patients satisfied six inclusion criteria: 1. Meeting criteria of the National Institute of Neurological Disease and Stroke/Alzheimer s Disease and Related Disorders Association for probable Alzheimer s disease (12) 2. Having minimal to moderate functional severity (a score of 15 or more on the Mini-Mental State Examination (MMSE) (13) 3. Having no lifetime history of other neurological or mental disorders 4. Taking no established and documented antidementia drugs other than donepezil (agents with possible antidementia properties, such as nonsteroidal antiinflammatory drugs, vitamins E, ginkgo biloba, and lecithin were allowed) 5. Having no evidence of focal brain lesions on a MRI 6. There being informed consent from patients and their relatives for determination of their apolipoprotein E (APOE) genotype The control group was selected among those who participated in the annual follow-up program between July 1993 and October Requirements for inclusion in the present study were the same as those for the donepezil follow-up participants except for the use of donepezil. Those who received anti-alzheimer drugs other than donepezil were not included in the present study. In this study, only baseline and 1-year follow-up data were used. Cognitive Functions The status of global cognitive function was assessed with the MMSE and the Alzheimer s Disease Assessment Scale (14). The Alzheimer s Disease Assessment Scale was administrated by neuropsychologists (along with the MRI examination) who were not involved in managing the patients at a 1-year interval (10 14 months). MRI Volumetry We directly measured the volume of the hippocampal formation on high spatial resolution three-dimensional spoiled-gradient echo images (15). The images were generated perpendicular to the anterior-posterior commissure plane that covers the whole calvaria with a 1.5-T MRI unit (Sign Advantage 5.x, General Electric Medical Systems, Milwaukee). The operating parameters were as follows: field of view=220 mm, matrix= , mm contiguous sections, TR=14 msec, TE=3 msec, and flip angle=20. The detailed hippocampal MRI volumetric procedure is described elsewhere (15). In brief, the MRI data set was transmitted to a computer from the MRI unit, and after an appropriate data conversion, it was analyzed by using the public domain Image version 1.62 program (developed at the National Institutes of Health and available on the Internet at nih-image/) with residential macro programs developed in our institute. Hippocampal formation volume in all subjects was measured by a single investigator (M.H.) who was blinded to 1) all clinical information, 2) the order (initial and follow-up) of MRIs, and 3) the time of enrollment. Before starting the measurement, the rater inspected the suitability of MRIs for hippocampal volumetry. If either one of the two MRIs obtained for a subject was unsuitable for volumetry because of motion artifacts or for any other technical reason, the subject was excluded from the study. For volumetry, we used a combination of semiautomatic segmentation-through-density thresholding and manual tracing, thereby lowering partial voluming and the observer s bias. The reliability and validity of volumetry have been established and described elsewhere (9, 15). The hippocampal formation was defined to include the pes hippocampi, digitationes hippocampi, alveus hippocampi, dentate gyrus, and subiculum (16 18). The boundary of the hippocampal formation was defined from the entire head of the hippocampus to the slice where the crus of the fornix was seen in full profile. The outline of the hippocampal formation together with the surrounding white matter and CSF was first traced with a manually guided mouse cursor, and subsequently, the gray matter of each structure was extracted by density thresholding set at a range between minimum and maximum pixel values. The maximum value was defined as the largest value for any pixel of the gray matter (represented by the caudate head). The minimum value was defined as one-half the sum of the mean pixel value of the gray matter and the mean value of CSF (represented by the lateral ventricle) (16). The slice volume of the hippocampal formation was obtained by automatically counting the number of pixels within the segmented regions and then multi
3 DONEPEZIL AND HIPPOCAMPAL ATROPHY TABLE 1. Demographic and Clinical Characteristics of Patients With Alzheimer s Disease Characteristic Apolipoprotein E (APOE) ε4 (N=35) Donepezil-Treated Group Control Group (N=19) (N=54) (N=50) (N=43) N N N N N N Sex Male Female (N=93) Mean SD Mean SD Mean SD Mean SD Mean SD Mean SD Age (years) Education (years) Duration of disease (months) Magnetic resonance imaging interval (days) Baseline score on Mini-Mental State Examination plying the number by the voxel size: 9([220/256] 2 [1.5= mm 3 ]). The average volume of the right and left hippocampal formations was used for the analysis. The test-retest reliability (kappa=0.98) was measured as an intraclass correlation coefficient derived from three repeated measurements by a single rater under blinded conditions in 10 randomly selected subjects. Coefficients of variation (standard deviation/mean, where standard deviation indicates square root value of the arithmetic mean of 10 variance estimates) were 2.84% and 2.78% for the right and left hippocampal formations, respectively. Determination of APOE Genotype The detailed method for APOE genotyping is described elsewhere (19). In brief, genomic DNA was extracted from peripheral blood with a Genomix DNA extraction kit (Talent Corp., Trieste, Italy) according to the manufacturer s protocol. The APOE genotype was determined by using polymerase chain reaction restriction fragment length polymorphism, according to the procedure described by Wenham and colleagues (20). Statistical Analysis The annual rate of hippocampal atrophy was defined as the percentage change, which was computed as baseline hippocampal formation volume minus 1-year hippocampal formation volume divided by baseline hippocampal formation volume ( 100). The change in cognitive decline was expressed as the difference (points) between the baseline and 1-year Alzheimer s Disease Assessment Scale scores. Because the allele is known to be specifically related to hippocampal atrophy in Alzheimer s disease (9, 21), the effect of donepezil on hippocampal atrophy is possibly influenced by the APOE genotype. Therefore, we used two-way analysis of variance, which included the effects of donepezil treatment (i.e., treated and untreated), APOE type (i.e., presence and absence of the allele), and their interaction. When the interaction term was not significant, the effects of the donepezil treatment were examined with a t test. When significant effects were found, they were further examined with analysis of covariance (ANCOVA) in which age, sex, disease duration, education, interval between the two MRI studies (days), APOE genotype, and baseline MMSE score were entered into the model as covariates. The level of significance was set at p<0.05 for all statistical analyses. Results Twelve of 77 patients who were initially enrolled in the donepezil follow-up program were dropped from the study. Seven withdrew their consent, two were institutionalized, and the remaining three withdrew for other reasons. Of the 65 patients who completed the entire procedure of the study, 11 were excluded because the quality of one of their two MRIs was unsuitable for volumetry. Thus, 54 patients remained in the treated group. Two patients did not receive the full, 1-year dosage of donepezil. One patient discontinued donepezil after 3 weeks because of adverse effects, and the other took the drug irregularly (receiving about 60% of the full dose). However, these patients were included in the primary analyses. Of the 108 patients who completed the entire procedure of the annual follow-up study, 15 patients were excluded because their MRIs were of poor quality. Thus, 93 patients remained in the control group. The background characteristics of both groups are summarized in Table 1. The treated and control groups were not significantly different in age, sex, education, disease duration, intervals between the first and second MRI, or baseline MMSE scores. Hippocampal volumes and Alzheimer s Disease Assessment Scale scores are summarized in Table 2. The effect of donepezil treatment on the change in Alzheimer s Disease Assessment Scale scores was significant (F=5.55, df=143, p<0.02), but neither the effect of the allele (F=3.64, df=143, p<0.06) nor the interaction term (F=0.32, df=143, p=0.57) was significant. The effects of donepezil treatment and the allele on the rate of hippocampal atrophy were significant (F=8.19, df=143, p=0.005, and F=5.29, df= 143, p<0.03, respectively), but the interaction term was not significant (F=0.08, df=143, p=0.78). In a further analysis, the mean annual rate of hippocampal atrophy in the treated group (mean=3.82%, SD=2.84%) was significantly lower than in the control group (mean=5.04%, SD=2.54%) (t= 2.7, df=145, p=0.008). In a one-way ANCOVA, where 678
4 HASHIMOTO, KAZUI, MATSUMOTO, ET AL. TABLE 2. Annual Change in Alzheimer s Disease Assessment Scale Score and Rate of Hippocampal Atrophy Among Patients With Alzheimer s Disease Apolipoprotein E (APOE) ε4 (N=35) Donepezil-Treated Group (N=19) (N=54) (N=50) Control Group (N=43) (N=93) Variable Mean SD Mean SD Mean SD Mean SD Mean SD Mean SD Baseline Alzheimer s Disease Assessment Scale score Annual change in Alzheimer s Disease Assessment Scale a Baseline hippocampal formation volume (mm 3 ) Annual hippocampal atrophy rate (%) a,b a Significant effect of treatment. b Significant effect of allele. age, sex, disease duration, education, MRI interval, APOE genotype, and baseline Alzheimer s Disease Assessment Scale score were entered into the model as covariates, the effect of donepezil on hippocampal atrophy remained significant (F=10.34, df=138, p=0.002). Even if the two patients who did not receive the full 1- year dosage of donepezil were excluded from the analyses, the results remained unchanged; donepezil treatment had significant effects on Alzheimer s Disease Assessment Scale score (F=4.37, df=141, p<0.04) and the rate of hippocampal atrophy (F=6.53, df=141, p<0.02), and the APOE ε4 allele had a significant effect on the rate of hippocampal atrophy (F=4.14, df=142, p<0.05). The mean annual rate of hippocampal atrophy in the treated group (mean=3.93%, SD=2.76%) was significantly lower than in the control group (mean=5.04%, SD=2.54%) (t= 2.4, df=143, p<0.02). Discussion In the present study, the mean annual decline in the Alzheimer s Disease Assessment Scale score in the control group (3.6 points) was significantly larger than in the treated group (0.8 points). Thus, these results are consistent with the results of previous long-term studies of donepezil (2, 3), and suggest that treatment with donepezil for 1 year was associated with a cognitive benefit. Moreover, donepezil seemingly slows the rate of hippocampal atrophy. The decrease in hippocampal volume in the treated patients (3.82%) was about 24% less than in the control patients (5.04%). The present results suggest that donepezil has both symptomatic and disease-progression slowing effects. The mean annual rate of hippocampal atrophy was significantly higher in the patients with the allele than in those without the allele, replicating our previous observation that the allele is specifically related to accelerated hippocampal pathology in Alzheimer s disease (9). On the other hand, for the rate of hippocampal atrophy and for the change in Alzheimer s Disease Assessment Scale, no significant interaction was noted between donepezil treatment and the APOE genotype. In a previous study, the effect of donepezil treatment did not appear to be affected by the APOE genotype (22). Our data are consistent with this observation. In recent studies, long-term donepezil treatment has been demonstrated to slow the decline in cognition and functional activities (2, 3), delay the admission to a nursing home (4), and reduce the decline in rcbf (5). However, these studies do not answer the question of whether the beneficial effects of donepezil are due to symptomatic suppression, which leaves the underlying disease process unaltered, or to neuroprotection modifying the disease process. Recently, one randomized, double-blind, placebo-controlled pilot study in patients with Alzheimer s disease demonstrated that donepezil-treated patients had significantly smaller mean decreases in total hippocampal volumes compared with placebo-treated patients. Although that study had limitations in that it included a relatively small number of patients and the period of drug treatment was short, our data are consistent with the results (23). Furthermore, two clinical trials, both open-label, placebo-controlled extension studies, have raised the possibility that cholinesterase inhibitors have slowing effects on both symptomatic and disease progression in Alzheimer s disease patients. In one study (24), the level of cognitive function in patients who were treated with placebo for 3 months, followed by 12 months of donepezil treatment, was lower than in patients who were treated with donepezil for all 15 months. In the other study (25), the level of cognitive function of the patients who were treated with placebo for 26 weeks, followed by 26 weeks of rivastigmine treatment, was lower than that in patients who were treated with rivastigmine for all 52 weeks. The inability to catch up in those in whom the treatment with 679
5 DONEPEZIL AND HIPPOCAMPAL ATROPHY cholinesterase inhibitors was postponed reminds us of a potential disease-modifying effect. A recent long-term randomized, double-blind trial (26) showed that no significant benefits were seen with donepezil compared with placebo in the institutionalization and progression of disability. In the study, there were no significant differences in behavioral symptoms, caregiver well-being, and caregiver time costs. On the other hand, statistically significant cognitive and functional effects were maintained over at least 2 years. Because many of the outcomes are influenced by the interaction of complex biological, social, and environmental factors, they might be inappropriate for assessing the neuroprotective effects of donepezil. To explain the neuroprotective effect of cholinesterase inhibitors, mechanisms based on beta-amyloid metabolism have been postulated. Accumulation of amyloid is one of the earliest changes in Alzheimer s disease pathology (27, 28) and may cause neuronal death in the CNS (29, 30). In vitro studies have demonstrated a link between cholinergic activation and beta-amyloid precursor protein metabolism. Wallace et al. (31) found evidence that lesions of the cholinergic nucleus basalis of Meynert increased the synthesis of beta-amyloid precursor protein in the cerebral cortex of rats. Wolf et al. (32), using human CNS neurons, found increased amyloid precursor protein secretion and decreased beta-amyloid protein production with carbachol stimulation of muscarinic receptors (32). These studies support a beneficial alteration in amyloid processing associated with cholinergic stimulation. Kihara et al. (33) examined the effects of nicotinic receptor agonists on amyloid beta cytotoxicity in cultured rat cortical neurons and found that nicotinic receptor stimulation may be able to protect neurons from degeneration induced by amyloid beta. Svensson and Nordberg (34) demonstrated that tacrine and donepezil at clinically relevant concentrations attenuated amyloid beta (25-35)-induced toxicity in rat pheochromocytoma PC12 cells. The neuroprotective effect was blocked by the presence of the nicotinic antagonists mecamylamine and tubocurarine, suggesting an intervention through nicotinic receptors. Our study has some limitations. First, because it was a comparative study with a historical control group rather than a randomized study, it suffers from several sources of bias. The groups are not comparable because of the selection of subjects who received the intervention (selection bias), the cointerventions and other medical management being received by the two groups were different (performance bias), and the methods of outcome measurement being used in the two groups were different (detection bias). Although there was no intention to select subjects for the control and treatment groups, patients who could not tolerate the initial doses of donepezil were not included in the donepezil follow-up program. This could have been a source of selection bias. However, we are unaware of any evidence that donepezil tolerance predicts disease progression. Because the control group in the present study was not concurrent but historical, there was a generation difference of several years between the groups. Although the generation difference was a possible source of selection and performance bias, the difference in the patients generation was not likely to affect the volumetric results, and the cointerventions and other medical management did not change throughout the first and second halves of the study period. Second, it has been recognized that open-label studies are not optimal. The fact that the investigators were not blinded to treatment might increase the donepezil effect. However, neither hippocampal volume nor the Alzheimer s Disease Assessment Scale score was a subjective outcome measure. Furthermore, in the present study, the Alzheimer s Disease Assessment Scale was administered by neuropsychologists who were unblinded but not involved in managing the patients, and MRI volumetry was made by an investigator who was blinded to all clinical information. Therefore, it was unlikely that detection bias affected the results of the rate of hippocampal atrophy or the Alzheimer s Disease Assessment Scale score in favor of the donepezil-treated group. Third, dropouts are a problem for this type of design and a possible source of exclusion bias. Simply ignoring everyone who has withdrawn from a clinical trial may bias the results, usually in favor of the intervention. Therefore, it is standard practice to analyze the results of comparative studies on an intention-to-treat basis. In the present study, two patients who did not take the full 1-year dosage of donepezil because of adverse events or poor compliance were included in the primary analyses. As a result, the patients background characteristics, such as age, sex, education, disease duration, disease severity, and MRI interval, were comparable between the two groups, and even after we controlled for these variables, the effect of donepezil on hippocampal atrophy remained unchanged. In any case, the significant difference of the rate of hippocampal atrophy was likely to be due to the intervention with donepezil. Although our findings should be confirmed by a randomized, controlled longterm trial in patients with Alzheimer s disease, it would be unethical to conduct such a study to extend the knowledge of donepezil. The present results suggest that donepezil has not only a symptomatic effect but also a neuroprotective effect. If donepezil does, in fact, influence disease progression, we need to modify our treatment strategies; donepezil is not an optional but rather a mandatory treatment for Alzheimer s disease and should be started in the prodromal or very early stage of the disease. Mild cognitive impairment is a condition that frequently progresses to Alzheimer s disease, which requires early diagnostic and therapeutic interventions. Donepezil, through its neuroprotective effect, could possibly inhibit progression from mild cognitive impairment to Alzheimer s disease. Further studies are needed to determine whether donepezil slows the progres
6 HASHIMOTO, KAZUI, MATSUMOTO, ET AL. sion from mild cognitive impairment to Alzheimer s disease. Hippocampal atrophy could be used as a surrogate marker of disease progression in such studies. Furthermore, the potential neuroprotective mechanism should be refined and exploited to enhance the drug s effectiveness in treating Alzheimer s disease. A better understanding of this mechanism may suggest strategies for designing improved drugs. Received June 11, 2004; revision received Sept. 1, 2004; accepted Sept. 10, From the Hyogo Institute for Aging Brain and Cognitive Disorders, Hyogo, Japan; Sawa Hospital at Toyonaka; the Department of Psychiatry and Behavior Science, Osaka University Graduate School of Medicine, Osaka, Japan; the Department of Psychiatry and Neurology, Kobe Graduate University School of Medicine, Hyogo, Japan; and the Department of Behavioral Neurology and Cognitive Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Japan. Address correspondence and reprint requests to Dr. Hashimoto, Sawa Hospital, Shiroyamacho, Toyonaka, Osaka, , Japan; qq257xk9@minos.ocn.ne.jp ( ). References 1. Rogers SL, Farlow MR, Doody RS, Mohs R, Friedhoff LT: A 24- week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer s disease. Neurology 1998; 50: Winblad B, Engedal K, Soininen H, Verhey F, Waldemar G, Wimo A, Wetterholm AL, Zhang R, Haglund A, Subbiah P (Donepezil Nordic Study Group): A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD. Neurology 2001; 57: Mohs RC, Doody RS, Morris JC, Ieni JR, Rogers SL, Perdomo CA, Pratt RD ( 312 Study Group): A 1-year, placebo-controlled preservation of function survival study of donepezil in AD patients. Neurology 2001; 57: Lopez OL, Becker JT, Wisniewski S, Saxton J, Kaufer DI, DeKosky ST: Cholinesterase inhibitor treatment alters the natural history of Alzheimer s disease. J Neurol Neurosurg Psychiatry 2002; 72: Nakano S, Asada T, Matsuda H, Uno M, Takasaki M: Donepezil hydrochloride preserves regional cerebral blood flow in patients with Alzheimer s disease. J Nucl Med 2001; 42: Braak H, Braak E: Pathology of Alzheimer s disease, in Neurodegenerative Disease. Edited by Calne DB. Philadelphia, WB Saunders, 1994, pp Laakso MP, Soininen H, Partanen K, Helkala EL, Hartikainen P, Vainio P, Hallikainen M, Hanninen T, Riekkinen PJ Sr: Volumes of hippocampus, amygdala and frontal lobes in the MRI-based diagnosis of early Alzheimer s disease: correlation with memory functions. J Neural Transm 1995; 9: Jack CR Jr, Petersen RC, O Brien PC, Tangalos EG: MR based hippocampal volumetry in the diagnosis of Alzheimer s disease. Neurology 1992; 42: Mori E, Lee K, Yasuda M, Hashimoto M, Kazui H, Hirono N, Matsui M: Accelerated hippocampal atrophy in Alzheimer s disease with apolipoprotein E ε4 allele. Ann Neurol 2002; 51: Jack CR Jr, Petersen RC, Xu Y, O Brien PC, Smith GE, Ivnik RJ, Tangalos EG, Kokmen E: Rate of medial temporal lobe atrophy in typical aging and Alzheimer s disease. Neurology 1998; 51: Imamura T, Hirono N, Hashimoto M, Shimomura T, Tanimukai S, Kazui H, Hanihara T, Mori E: Clinical diagnosis of dementia with Lewy bodies in a Japanese dementia registry. Dement Geriatr Cogn Disord 1999; 10: McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: Clinical diagnosis of Alzheimer s disease: report of the NINCDS-ADRDA Work Group under the auspices of the Department of Health and Human Services Task Force on Alzheimer s Disease. Neurology 1984; 34: Folstein MF, Folstein SE, McHugh PR: Mini-Mental State : a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: Mohs RC, Rosen WG, Davis KL: The Alzheimer s Disease Assessment Scale: an instrument for assessing treatment efficacy. Psychopharmacol Bull 1983; 19: Mori E, Yoneda Y, Yamashita H, Hirono N, Ikeda M, Yamadori A: Medial temporal structures related to memory impairment in Alzheimer s disease: an MRI volumetric study. J Neurol Neurosurg Psychiatry 1997; 63: Lencz T, McCarthy G, Bronen RA, Scott TM, Inserni JA, Sass KJ, Novelly RA, Kim JH, Spencer DD: Quantitative magnetic resonance imaging in temporal lobe epilepsy: relationship to neuropathology and neuropsychological function. Ann Neurol 1992; 31: Lehéricy S, Baulac M, Chiras J, Pierot L, Martin N, Pillon B, Deweer B, Dubois B, Marsault C: Amygdalohippocampal MR volume measurement in the early stages of Alzheimer disease. Am J Neuroradiol 1994; 15: Jack CR Jr: MRI-based hippocampal volume measurements in epilepsy. Epilepsia 1994; 35(suppl 6): Yasuda M, Maeda K, Shimada K, Kakigi T, Mori E, Nakai M, Nishio H, Tanaka C: Apolipoprotein E ε4 allele and gender difference in risk of Alzheimer s disease. Alzheimer Res 1995; 1: Wenham PR, Price WH, Blandell G: Apolipoprotein E genotyping by one-stage PCR. Lancet 1991; 337: Hashimoto M, Yasuda M, Tanimukai S, Matsui M, Hirono N, Kazui H, Mori E: Apolipoprotein E ε4 and the pattern of regional brain atrophy in Alzheimer s disease. Neurology 2001; 57: Greenberg SM, Tennis MK, Brown LB, Gomez-Isla T, Hayden DL, Schoenfeld DA, Walsh KL, Corwin C, Daffner KR, Friedman P, Meadows ME, Sperling RA, Growdon JH: Donepezil therapy in clinical practice: a randomized crossover study. Arch Neurol 2000; 57: Krishnan KR, Charles HC, Doraiswamy PM, Mintzer J, Weisler R, Yu X, Perdomo C, Ieni JR, Rogers S: Randomized, placebo-controlled trial of the effects of donepezil on neuronal markers and hippocampal volumes in Alzheimer s disease. Am J Psychiatry 2003; 160: Doody RS, Geldmacher DS, Gordon B, Perdomo CA, Pratt RD (Donepezil Study Group): Open-label, multicenter, phase 3 extension study of the safety and efficacy of donepezil in patients with Alzheimer disease. Arch Neurol 2001; 58: Farlow M, Anand R, Messina J Jr, Hartman R, Veach J: A 52- week study of the efficacy of rivastigmine in patients with mild to moderately severe Alzheimer s disease. Eur Neurol 2000; 44: Courtney C, Farrell D, Gray R, Hills R, Lynch L, Sellwood E, Edwards S, Hardyman W, Raftery J, Crome P, Lendon C, Shaw H, Bentham P (AD2000 Collaborative Group): Long-term donepezil treatment in 565 patients with Alzheimer s disease (AD2000): randomized double-blind trial. Lancet 2004; 363: Hardy JA, Allsop D: Amyloid deposition as the central event in the aetiology of Alzheimer s disease. Trends Pharmacol Sci 1991; 12: Hardy JA, Higgins GA: Alzheimer s disease: the amyloid cascade hypothesis. Science 1992; 256:
7 DONEPEZIL AND HIPPOCAMPAL ATROPHY 29. Yankner BA, Duffy LK, Kirschner DA: Neurotrophic and neurotoxic effects of amyloid beta protein: reversal by tachykinin neuropeptides. Science 1990; 250: Loo DT, Copani A, Pike CJ, Whittemore ER, Walencewicz AJ, Cotman CW: Apoptosis is induced by beta-amyloid in cultured central nervous system neurons. Proc Natl Acad Sci USA 1993; 90: Wallace W, Ahlers ST, Gotlib J, Bragin V, Sugar J, Gluck R, Shea PA, Davis KL, Haroutunian V: Amyloid precursor protein in the cerebral cortex is rapidly and persistently induced by loss of subcortical innervation. Proc Natl Acad Sci USA 1993; 90: Wolf BA, Wertkin AM, Jolly YC, Yasuda RP, Wolfe BB, Konrad RJ, Manning D, Ravi S, Williamson JR, Lee VM: Muscarinic regulation of Alzheimer s disease amyloid precursor protein secretion and amyloid beta-protein production in human neuronal NT2N cells. J Biol Chem 1995; 270: Kihara T, Shimohara S, Sawada H, Kimura J, Kume T, Kochiyama H, Maeda T, Akaike A: Nicotinic receptor stimulation protects neurons against beta-amyloid toxicity. Ann Neurol 1997; 42: Svensson AL, Nordberg A: Tacrine and donepezil attenuate the neurotoxic effect of A beta(25-35) in rat PC12 cells. Neuroreport 1998; 9:
Accelerated Memory Decline in Alzheimer s Disease With Apolipoprotein e4 Allele
Accelerated Memory Decline in Alzheimer s Disease With Apolipoprotein e4 Allele Nobutsugu Hirono, M.D., Ph.D. Mamoru Hashimoto, M.D., Ph.D. Minoru Yasuda, M.D., Ph.D. Hirokazu Kazui, M.D., Ph.D. Etsuro
More informationC holinomimetic drugs constitute the first line of treatment
310 PAPER Cholinesterase inhibitor treatment alters the natural history of Alzheimer s disease O L Lopez, J T Becker, S Wisniewski, J Saxton, D I Kaufer, S T DeKosky... See end of article for authors affiliations...
More informationNew life Collage of nursing Karachi
New life Collage of nursing Karachi Presenter: Zafar ali shah Faculty: Raja khatri Subject: Pathophysiology Topic :Alzheimer s Disease Post RN BScN semester 2 nd Objective Define Alzheimer s Describe pathophysiology
More informationAnosognosia, or loss of insight into one s cognitive
REGULAR ARTICLES Anosognosia Is a Significant Predictor of Apathy in Alzheimer s Disease Sergio E. Starkstein, M.D., Ph.D. Simone Brockman, M.A. David Bruce, M.D. Gustavo Petracca, M.D. Anosognosia and
More informationSatoh M. 1, Ishikawa H. 1, Meguro K. 1,2, Kasuya M. 1, Ishii H. 3, and Yamaguchi S. 2
CYRIC Annual Report 2009 VIII 15. Occipital Glucose Metabolic Decrease by Donepezil Treatment Correlated with the Improvement of Visual Hallucinations in Dementia with Lewy Bodies: the Osaki-Tajiri Project
More informationAlzheimer's disease (AD), also known as Senile Dementia of the Alzheimer Type (SDAT) or simply Alzheimer s is the most common form of dementia.
CHAPTER 3 Alzheimer's disease (AD), also known as Senile Dementia of the Alzheimer Type (SDAT) or simply Alzheimer s is the most common form of dementia. This incurable, degenerative, terminal disease
More informationSUPPLEMENTARY INFORMATION In format provided by Frank et al. (JULY 2010)
Table 1 Imaging bios for Alzheimer s Visual rating High correlation with Multicenter studies have Accuracy for longitudinal hippocampus volume (R 2 been performed, but changes only at chance about 0.9,
More informationIt has been demonstrated in both naturalistic and experimental
Amygdalar Volume and Emotional Memory in Alzheimer s Disease Etsuro Mori, M.D., Ph.D., Manabu Ikeda, M.D., Ph.D., Nobutsugu Hirono, M.D., Ph.D., Hajime Kitagaki, M.D., Ph.D., Toru Imamura, M.D., and Tatsuo
More informationSupplementary Online Content
Supplementary Online Content Hooshmand B, Magialasche F, Kalpouzos G, et al. Association of vitamin B, folate, and sulfur amino acids with brain magnetic resonance imaging measures in older adults: a longitudinal
More informationEstimating the Validity of the Korean Version of Expanded Clinical Dementia Rating (CDR) Scale
Estimating the Validity of the Korean Version of Expanded Clinical Dementia Rating (CDR) Scale Seong Hye Choi, M.D.*, Duk L. Na, M.D., Byung Hwa Lee, M.A., Dong-Seog Hahm, M.D., Jee Hyang Jeong, M.D.,
More informationWHAT IS DEMENTIA? An acquired syndrome of decline in memory and other cognitive functions sufficient to affect daily life in an alert patient
DEMENTIA WHAT IS DEMENTIA? An acquired syndrome of decline in memory and other cognitive functions sufficient to affect daily life in an alert patient Progressive and disabling Not an inherent aspect of
More informationALZHEIMER S DISEASE. Mary-Letitia Timiras M.D. Overlook Hospital Summit, New Jersey
ALZHEIMER S DISEASE Mary-Letitia Timiras M.D. Overlook Hospital Summit, New Jersey Topics Covered Demography Clinical manifestations Pathophysiology Diagnosis Treatment Future trends Prevalence and Impact
More informationReceived: 27 Apr 2009 Revisions requested: 18 Jun 2009 Revisions received: 1 Oct 2009 Accepted: 21 Oct 2009 Published: 21 Oct 2009
Research Persistent treatment with cholinesterase inhibitors and/or memantine slows clinical progression of Alzheimer disease Susan D Rountree 1, Wenyaw Chan 2, Valory N Pavlik 3, Eveleen J Darby 1, Samina
More informationLong-term associations between cholinesterase inhibitors and memantine use and health outcomes among patients with Alzheimer s disease
Alzheimer s & Dementia 9 (2013) 733 740 Long-term associations between cholinesterase inhibitors and memantine use and health outcomes among patients with Alzheimer s disease Carolyn W. Zhu a, *, Elayne
More information8/14/2018. The Evolving Concept of Alzheimer s Disease. Epochs of AD Research. Diagnostic schemes have evolved with the research
The Evolving Concept of Alzheimer s Disease David S. Geldmacher, MD, FACP Warren Family Endowed Chair in Neurology Department of Neurology UAB School of Medicine Epochs of AD Research Epoch Years Key Event
More informationErin Cullnan Research Assistant, University of Illinois at Chicago
Dr. Moises Gaviria Distinguished Professor of Psychiatry, University of Illinois at Chicago Director of Consultation Liaison Service, Advocate Christ Medical Center Director of the Older Adult Program,
More informationORIGINAL CONTRIBUTION. Response of Patients With Alzheimer Disease to Rivastigmine Treatment Is Predicted by the Rate of Disease Progression
ORIGINAL CONTRIBUTION Response of Patients With Alzheimer Disease to Rivastigmine Treatment Is Predicted by the Rate of Disease Progression Martin R. Farlow, MD; Ann Hake, MD; John Messina, PharmD; Richard
More informationQuantitative analysis for a cube copying test
86 99 103 2010 Original Paper Quantitative analysis for a cube copying test Ichiro Shimoyama 1), Yumi Asano 2), Atsushi Murata 2) Naokatsu Saeki 3) and Ryohei Shimizu 4) Received September 29, 2009, Accepted
More informationYin-Hui Siow MD, FRCPC Director of Nuclear Medicine Southlake Regional Health Centre
Yin-Hui Siow MD, FRCPC Director of Nuclear Medicine Southlake Regional Health Centre Today Introduction to CT Introduction to MRI Introduction to nuclear medicine Imaging the dementias The Brain ~ 1.5
More informationRegulatory Challenges across Dementia Subtypes European View
Regulatory Challenges across Dementia Subtypes European View Population definition including Early disease at risk Endpoints in POC studies Endpoints in pivotal trials 1 Disclaimer No CoI The opinions
More informationBrain imaging for the diagnosis of people with suspected dementia
Why do we undertake brain imaging in dementia? Brain imaging for the diagnosis of people with suspected dementia Not just because guidelines tell us to! Exclude other causes for dementia Help confirm diagnosis
More informationUse of Structural Magnetic Resonance Imaging to Predict Who Will Get Alzheimer s Disease
Use of Structural Magnetic Resonance Imaging to Predict Who Will Get Alzheimer s Disease Ronald J. Killiany, PhD,* Teresa Gomez-Isla, MD, PhD, Mark Moss, PhD,* Ron Kikinis, MD, Tamas Sandor, PhD, Ferenc
More informationORIGINAL CONTRIBUTION. Application of Automated Medial Temporal Lobe Atrophy Scale to Alzheimer Disease
ORIGINAL CONTRIBUTION Application of Automated Medial Temporal Lobe Atrophy Scale to Alzheimer Disease Basil H. Ridha, MRCP; Josephine Barnes, MA, PhD; Laura A. van de Pol, MD; Jonathan M. Schott, MD,
More informationRESEARCH AND PRACTICE IN ALZHEIMER S DISEASE VOL 10 EADC OVERVIEW B. VELLAS & E. REYNISH
EADC BRUNO VELLAS 14/01/05 10:14 Page 1 EADC OVERVIEW B. VELLAS & E. REYNISH (Toulouse, France, EU) Bruno Vellas: The European Alzheimer's Disease Consortium is a European funded network of centres of
More informationThe current state of healthcare for Normal Aging, Mild Cognitive Impairment, & Alzheimer s Disease
The current state of healthcare for Normal Aging, g, Mild Cognitive Impairment, & Alzheimer s Disease William Rodman Shankle, MS MD FACP Director, Alzheimer s Program, Hoag Neurosciences Institute Neurologist,
More informationTGF-ß1 pathway as a new pharmacological target for neuroprotection in AD. Filippo Caraci
Department of Clinical and Molecular Biomedicine Section of Pharmacology and Biochemistry Department of Educational Sciences University of Catania TGF-ß1 pathway as a new pharmacological target for neuroprotection
More informationMild Cognitive Impairment
Mild Cognitive Impairment Victor W. Henderson, MD, MS Departments of Health Research & Policy (Epidemiology) and of Neurology & Neurological Sciences Stanford University Director, Stanford Alzheimer s
More informationORIGINAL CONTRIBUTION. Comparison of the Short Test of Mental Status and the Mini-Mental State Examination in Mild Cognitive Impairment
ORIGINAL CONTRIBUTION Comparison of the Short Test of Mental Status and the Mini-Mental State Examination in Mild Cognitive Impairment David F. Tang-Wai, MDCM; David S. Knopman, MD; Yonas E. Geda, MD;
More informationDrugs for dementia: the first year
The Ulster Medical Journal, Volume 69, No. 2, pp. 123-127, November 2000. Drugs for dementia: the first year An audit of prescribing practice G McGirr, S A Compton Accepted 12 September 2000 SUMMARY In
More information.. Mini-Mental State Examination MMSE TPQ
Cloninger Tridimensional Personality Questionnaire TPQ Cloninger.... Mini-Mental State Examination MMSE Tridimensional Personality Questionnaire TPQ : U=., p
More informationMild Cognitive Impairment (MCI)
October 19, 2018 Mild Cognitive Impairment (MCI) Yonas E. Geda, MD, MSc Professor of Neurology and Psychiatry Consultant, Departments of Psychiatry & Psychology, and Neurology Mayo Clinic College of Medicine
More informationConfusional state. Digit Span. Mini Mental State Examination MMSE. confusional state MRI
10 304 29 3 confusional state MRI 29 3 304 311 2009 Key Words memory test attention brain region causative disease subcortical dementia 1 Confusional state Digit Span 1 1 5 4 Mini Mental State Examination
More informationCLINICAL TRIALS SECTION EDITOR: IRA SHOULSON, MD. Efficacy of Donepezil in Early-Stage Alzheimer Disease
CLINICAL TRIALS SECTION EDITOR: IRA SHOULSON, MD Efficacy of Donepezil in Early-Stage Alzheimer Disease A Randomized Placebo-Controlled Trial Ben Seltzer, MD; Parvaneh Zolnouni, MD; Margarita Nunez, MD;
More informationNew diagnostic criteria for Alzheimer s disease and mild cognitive impairment for the practical neurologist
New diagnostic criteria for Alzheimer s disease and mild cognitive impairment for the practical neurologist Andrew E Budson, 1,2 Paul R Solomon 2,3 1 Center for Translational Cognitive Neuroscience, VA
More informationMagnetic resonance imaging of the entorhinal cortex and hippocampus in mild cognitive impairment and Alzheimer s disease
J Neurol Neurosurg Psychiatry 2001;71:441 447 441 Magnetic Resonance Unit, Veterans AVairs Medical Center (114M), University of California, San Francisco 4150, Clement Street, San Francisco, CA 94121,
More informationNIH Public Access Author Manuscript Am J Geriatr Psychiatry. Author manuscript; available in PMC 2012 January 1.
NIH Public Access Author Manuscript Published in final edited form as: Am J Geriatr Psychiatry. 2011 January ; 19(1): 4 12. doi:10.1097/jgp.0b013e3181d6c245. Change in hippocampal volume on magnetic resonance
More informationSubject Index. Band of Giacomini 22 Benton Visual Retention Test 66 68
Subject Index Adams, R.D. 4 Addenbrooke s Cognitive Examination 101 Alzheimer s disease clinical assessment histological imaging 104 neuroimaging 101 104 neuropsychological assessment 101 clinical presentation
More informationA Dynamic Model of Care for Late Onset Cognitive Impairment. Linda CW Lam Department of Psychiatry The Chinese University of Hong Kong
A Dynamic Model of Care for Late Onset Cognitive Impairment Linda CW Lam Department of Psychiatry The Chinese University of Hong Kong Outline The pathogenesis of Late life cognitive impairment A framework
More informationManagement of cognition and function: new results from the clinical trials programme of Aricept (donepezil HCl)
International Journal of Neuropsychopharmacology (2000), 3 (Supplement 2), S13 S20. Copyright 2000 CINP Management of cognition and function: new results from the clinical trials programme of Aricept (donepezil
More informationDiagnosis and Treatment of Alzhiemer s Disease
Diagnosis and Treatment of Alzhiemer s Disease Roy Yaari, MD, MAS Director, Memory Disorders Clinic, Banner Alzheimer s Institute 602-839-6900 Outline Introduction Alzheimer s disease (AD)Guidelines -revised
More informationCortical hypoperfusion in Parkinson's disease assessed with arterial spin labeling MRI
Cortical hypoperfusion in Parkinson's disease assessed with arterial spin labeling MRI Poster No.: C-0609 Congress: ECR 2013 Type: Scientific Exhibit Authors: S. Aoki, K. Kamagata, Y. Motoi, K. Kamiya,
More informationSupplementary online data
THELANCETNEUROLOGY-D-07-00083 Supplementary online data MRI assessments MRI at each site included a volumetric spoiled gradient echo (T1-weighted) sequence with slice partition thickness of 1 5 mm or less
More informationFully-automated volumetric MRI with normative ranges: Translation to clinical practice
Behavioural Neurology 21 (2009) 21 28 21 DOI 10.3233/BEN-2009-0226 IOS Press Fully-automated volumetric MRI with normative ranges: Translation to clinical practice J.B. Brewer Department of Radiology and
More informationVisual Rating Scale Reference Material. Lorna Harper Dementia Research Centre University College London
Visual Rating Scale Reference Material Lorna Harper Dementia Research Centre University College London Background The reference materials included in this document were compiled and used in relation to
More informationCASE 49. What type of memory is available for conscious retrieval? Which part of the brain stores semantic (factual) memories?
CASE 49 A 43-year-old woman is brought to her primary care physician by her family because of concerns about her forgetfulness. The patient has a history of Down syndrome but no other medical problems.
More informationFact Sheet Alzheimer s disease
What is Alzheimer s disease Fact Sheet Alzheimer s disease Alzheimer s disease, AD, is a progressive brain disorder that gradually destroys a person s memory and ability to learn, reason, make judgements,
More informationReview Article Broader Considerations of Higher Doses of Donepezil in the Treatment of Mild, Moderate, and Severe Alzheimer s Disease
International Alzheimer s Disease Volume 2012, Article ID 707468, 4 pages doi:10.1155/2012/707468 Review Article Broader Considerations of Higher Doses of Donepezil in the Treatment of Mild, Moderate,
More informationTreatment of AD with Stabilized Oral NADH: Preliminary Findings
MS # 200 000 128 Treatment of AD with Stabilized Oral NADH: Preliminary Findings G.G. Kay, PhD, V. N. Starbuck, PhD and S. L. Cohan, MD, PhD Department of Neurology, Georgetown University School of Medicine
More informationMorphology of the Inner Structure of the Hippocampal Formation in Alzheimer Disease
AJNR Am J Neuroradiol 24:1575 1581, September 2003 Morphology of the Inner Structure of the Hippocampal Formation in Alzheimer Disease Michito Adachi, Shinobu Kawakatsu, Takaaki Hosoya, Koichi Otani, Tsuguo
More informationDelirium & Dementia. Nicholas J. Silvestri, MD
Delirium & Dementia Nicholas J. Silvestri, MD Outline Delirium vs. Dementia Neural pathways relating to consciousness Encephalopathy Stupor Coma Dementia Delirium vs. Dementia Delirium Abrupt onset Lasts
More informationImaging of Alzheimer s Disease: State of the Art
July 2015 Imaging of Alzheimer s Disease: State of the Art Neir Eshel, Harvard Medical School Year IV Outline Our patient Definition of dementia Alzheimer s disease Epidemiology Diagnosis Stages of progression
More informationAlzheimer s Management: A Technical Solution for Neurologists, Patients and Caregivers
American Scientific Research Journal for Engineering, Technology, and Sciences (ASRJETS) ISSN (Print) 2313-4410, ISSN (Online) 2313-4402 Global Society of Scientific Research and Researchers http://asrjetsjournal.org/
More informationNeuroimaging for Diagnosis of Psychiatric Disorders
Psychiatric Disorder Neuroimaging for Diagnosis of Psychiatric Disorders JMAJ 45(12): 538 544, 2002 Yoshio HIRAYASU Associate Professor, Department of Neuropsychiatry Kyorin University School of Medicine
More informationSupplementary Online Content
Supplementary Online Content Gregg NM, Kim AE, Gurol ME, et al. Incidental cerebral microbleeds and cerebral blood flow in elderly individuals. JAMA Neurol. Published online July 13, 2015. doi:10.1001/jamaneurol.2015.1359.
More informationHOW TO PREVENT COGNITIVE DECLINE.AT MCI STAGE?
EAMA CORE CURRICULUM HOW TO PREVENT COGNITIVE DECLINE.AT MCI STAGE? Sofia Duque Orthogeriatric Unit São Francisco Xavier Hospital Occidental Lisbon Hospital Center University Geriatric Unit, Faculty of
More informationTerm Paper: Ginkgo Biloba s Influence on Memory and Cognition
1 Term Paper: Ginkgo Biloba s Influence on Memory and Cognition 2 Introduction The aging process is inevitable. Over time our bodies and the functions they provide start to decline in many aspects. Cognitive
More informationDementia. Stephen S. Flitman, MD Medical Director 21st Century Neurology
Dementia Stephen S. Flitman, MD Medical Director 21st Century Neurology www.neurozone.org Dementia is a syndrome Progressive memory loss, plus Progressive loss of one or more cognitive functions: Language
More informationBehavioral and psychological symptoms of dementia characteristic of mild Alzheimer patients
Blackwell Science, LtdOxford, UKPCNPsychiatry and Clinical Neurosciences1323-13162005 Blackwell Publishing Pty Ltd593274279Original ArticleDementia and mild AlzheimersJ. Shimabukuro et al. Psychiatry and
More informationRole of TDP-43 in Non-Alzheimer s and Alzheimer s Neurodegenerative Diseases
Role of TDP-43 in Non-Alzheimer s and Alzheimer s Neurodegenerative Diseases Keith A. Josephs, MD, MST, MSc Professor of Neurology 13th Annual Mild Cognitive Impairment (MCI) Symposium: Alzheimer and Non-Alzheimer
More informationPublished February 2, 2012 as /ajnr.A2935
Published February 2, 2012 as 10.3174/ajnr.A2935 ORIGINAL RESEARCH H. Matsuda S. Mizumura K. Nemoto F. Yamashita E. Imabayashi N. Sato T. Asada Automatic Voxel-Based Morphometry of Structural MRI by SPM8
More informationMentis Cura November
Mentis Cura November 29 2012 www.mentiscura.com New Facts on Alzheimer s Death rank nr. 2-5 in western countries Fastest growing disease in: Cost Incedence Death rate People with Alzheimer s 2012 36 million
More informationAn integrated natural disease progression model of nine cognitive and biomarker endpoints in patients with Alzheimer s Disease
An integrated natural disease progression model of nine cognitive and biomarker endpoints in patients with Alzheimer s Disease Angelica Quartino 1* Dan Polhamus 2*, James Rogers 2, Jin Jin 1 212, Genentech
More informationAlzheimer s Disease without Dementia
Alzheimer s Disease without Dementia Dr Emer MacSweeney CEO & Consultant Neuroradiologist Re:Cognition Health London Osteopathic Society 13 September 2016 Early diagnosis of Alzheimer s Disease How and
More informationORIGINAL CONTRIBUTION. The Spectrum of Behavioral Responses to Cholinesterase Inhibitor Therapy in Alzheimer Disease
ORIGINAL CONTRIBUTION The Spectrum of Behavioral Responses to Cholinesterase Inhibitor Therapy in Alzheimer Disease Michael S. Mega, MD, PhD; Donna M. Masterman, MD; Susan M. O Connor, RNC; Terry R. Barclay,
More informationHow can the new diagnostic criteria improve patient selection for DM therapy trials
How can the new diagnostic criteria improve patient selection for DM therapy trials Amsterdam, August 2015 Bruno Dubois Head of the Dementia Research Center (IMMA) Director of INSERM Research Unit (ICM)
More informationfmri and Voxel-based Morphometry in Detection of Early Stages of Alzheimer's Disease
fmri and Voxel-based Morphometry in Detection of Early Stages of Alzheimer's Disease Andrey V. Sokolov 1,3, Sergey V. Vorobyev 2, Aleksandr Yu. Efimtcev 1,3, Viacheslav S. Dekan 1,3, Gennadiy E. Trufanov
More informationIntroduction, use of imaging and current guidelines. John O Brien Professor of Old Age Psychiatry University of Cambridge
Introduction, use of imaging and current guidelines John O Brien Professor of Old Age Psychiatry University of Cambridge Why do we undertake brain imaging in AD and other dementias? Exclude other causes
More informationPocket Reference to Alzheimer s Disease Management
Pocket Reference to Alzheimer s Disease Management Pocket Reference to Alzheimer s Disease Management Anna Burke, MD Geriatric Psychiatrist, Dementia Specialist Geri R Hall, PhD, ARNP, GCNS, FAAN Advanced
More informationDifferential Diagnosis of Alzheimer s Disease and Other Types of Dementia with Development of Neuroimaging Techniques (PET, SPECT, and MRI)
www.jmscr.igmpublication.org Impact Factor 1.1147 ISSN (e)-2347-176x Differential Diagnosis of Alzheimer s Disease and Other Types of Dementia with Development of Neuroimaging Techniques (PET, SPECT, and
More informationBaseline Characteristics of Patients Attending the Memory Clinic Serving the South Shore of Boston
Article ID: ISSN 2046-1690 Baseline Characteristics of Patients Attending the www.thealzcenter.org Memory Clinic Serving the South Shore of Boston Corresponding Author: Dr. Anil K Nair, Chief of Neurology,
More informationThe most common cause of dementia is Alzheimer disease.
ORIGINAL RESEARCH A.J. Bastos-Leite J.H. van Waesberghe A.L. Oen W.M. van der Flier P. Scheltens F. Barkhof Hippocampal Sulcus Width and Cavities: Comparison Between Patients with Alzheimer Disease and
More informationMen and women are affected Male and Female larger amounts of intracranial CSF
Male and Female Sensitivity to Alcohol-Induced Brain Damage Daniel W. Hommer, M.D. are more vulnerable than men to many of the medical consequences of alcohol use. Although research has shown that male
More informationWe should not distinguish between symptomatic and disease-modifying treatments in Alzheimer s disease drug development
Alzheimer s & Dementia 4 (2008) S21 S25 We should not distinguish between symptomatic and disease-modifying treatments in Alzheimer s disease drug development Rachelle S. Doody* Baylor College of Medicine,
More information(anisotropic diffusion) (fractional anisotropy FA)
2 3 3 1 020-8505 19-1 2 020-8505 19-1 3 020-0173 348-58 Alzheimer(AD) 3). AD PETSPECTstatistical parametric mapping (SPM) 4), 56) PETMRI (anisotropic diffusion) (fractional anisotropyfa) 710) PETMRI (rcbf)(rcmr0
More informationEfficacy of Donepezil Treatment in Alzheimer Patients with and without Subcortical Vascular Lesions
Short Communication Pharmacology 2004;72:1 5 DOI: 10.1159/000078625 Received: January 27, 2004 Accepted after revision: February 23, 2004 Efficacy of Donepezil Treatment in Alzheimer Patients with and
More informationApolipoprotein E ε4 Allele and Whole Brain Atrophy in Late-Onset Alzheimer s Disease
YASUDA, APOLIPOPROTEIN Am J Psychiatry MORI, KITAGAKI, 155:6, E ε4 ALLELE June ET 1998 AL. Apolipoprotein E ε4 Allele and Whole Brain Atrophy in Late-Onset Alzheimer s Disease Minoru Yasuda, M.D., Etsuro
More informationAlzheimer disease is the most common cause of dementia in
ORIGINAL RESEARCH BRAIN Automated Segmentation of Hippocampal Subfields in Drug-Naïve Patients with Alzheimer Disease H.K. Lim, S.C. Hong, W.S. Jung, K.J. Ahn, W.Y. Won, C. Hahn, I.S. Kim, and C.U. Lee
More informationGeneral introduction
1 General introduction 10 Chapter 1 General Introduction Dementia Dementia is defined as an acquired impairment of cognitive function in at least two domains, including memory, which interferes with normal
More informationRound table: Moderator; Fereshteh Sedaghat, MD, PhD Brain Mapping in Dementias and Non-invasive Neurostimulation
Round table: Moderator; Fereshteh Sedaghat, MD, PhD Brain Mapping in Dementias and Non-invasive Neurostimulation 1. Reflection of Mild Cognitive Impairment (MCI) and Dementias by Molecular Imaging, PET
More informationAlzheimer s Disease. Clinical characteristics of late-onset Alzheimer s disease (LOAD) A/Prof David Darby
Alzheimer s Disease Clinical characteristics of late-onset Alzheimer s disease (LOAD) A/Prof David Darby Florey Institute of Neuroscience and Mental Health 28-6-2013 The burden of late-onset Alzheimer
More informationA lzheimer s disease has many neuropsychiatric manifestations
1396 PAPER Right prosubiculum amyloid plaque density correlates with anosognosia in Alzheimer s disease G A Marshall, D I Kaufer, O L Lopez, G R Rao, R L Hamilton, S T DeKosky... See end of article for
More informationDISCLOSURES. Objectives. THE EPIDEMIC of 21 st Century. Clinical Assessment of Cognition: New & Emerging Tools for Diagnosing Dementia NONE TO REPORT
Clinical Assessment of Cognition: New & Emerging Tools for Diagnosing Dementia DISCLOSURES NONE TO REPORT Freddi Segal Gidan, PA, PhD USC Keck School of Medicine Rancho/USC California Alzheimers Disease
More informationNeuropathology of Neurodegenerative Disorders Prof. Jillian Kril
Neurodegenerative disorders to be discussed Alzheimer s disease Lewy body diseases Frontotemporal dementia and other tauopathies Huntington s disease Motor Neuron Disease 2 Neuropathology of neurodegeneration
More informationSupplementary Online Content
Supplementary Online Content Redlich R, Opel N, Grotegerd D, et al. Prediction of individual response to electroconvulsive therapy via machine learning on structural magnetic resonance imaging data. JAMA
More informationFour Tissue Segmentation in ADNI II
Four Tissue Segmentation in ADNI II Charles DeCarli, MD, Pauline Maillard, PhD, Evan Fletcher, PhD Department of Neurology and Center for Neuroscience, University of California at Davis Summary Table of
More informationBiomarkers Workshop In Clinical Trials Imaging for Schizophrenia Trials
Biomarkers Workshop In Clinical Trials Imaging for Schizophrenia Trials Research focused on the following areas Brain pathology in schizophrenia and its modification Effect of drug treatment on brain structure
More informationDementia Update. October 1, 2013 Dylan Wint, M.D. Cleveland Clinic Lou Ruvo Center for Brain Health Las Vegas, Nevada
Dementia Update October 1, 2013 Dylan Wint, M.D. Cleveland Clinic Lou Ruvo Center for Brain Health Las Vegas, Nevada Outline New concepts in Alzheimer disease Biomarkers and in vivo diagnosis Future trends
More informationAlzheimer's Disease. Dementia
Alzheimer's Disease Victor W. Henderson, MD, MS Departments of Health Research & Policy (Epidemiology) and of Neurology & Neurological Sciences Stanford University Director, Stanford Alzheimer s Disease
More informationKnown as both a thief and murderer,
&A Dementia Drugs: When Should They Be Stopped? Ron Keren, MD, FRCPC As presented at the University of Toronto s Primary Care Conference, Toronto, Ontario (May 25) Known as both a thief and murderer, Alzheimer
More informationBiogen, Cambridge, MA, USA; 2 Cytel, Cambridge, MA, USA; 3 Neurimmune, Schlieren-Zurich, and University of Zurich, Switzerland
Aducanumab 36-Month Data From PRIME: A Randomized, Double-Blind, Placebo-Controlled Phase 1b Study in Patients With Prodromal or Mild Alzheimer s Disease Samantha Budd Haeberlein, PhD 1, Sarah Gheuens,
More informationSupplemental Data. Inclusion/exclusion criteria for major depressive disorder group and healthy control group
1 Supplemental Data Inclusion/exclusion criteria for major depressive disorder group and healthy control group Additional inclusion criteria for the major depressive disorder group were: age of onset of
More informationT he ability to consciously learn and retain new information
44 PAPER fmri studies of associative encoding in young and elderly controls and mild Alzheimer s disease R A Sperling, J F Bates, E F Chua, A J Cocchiarella, D M Rentz, B R Rosen, D L Schacter, M S Albert...
More informationWe are IntechOpen, the world s leading publisher of Open Access books Built by scientists, for scientists. International authors and editors
We are IntechOpen, the world s leading publisher of Open Access books Built by scientists, for scientists 4,100 116,000 120M Open access books available International authors and editors Downloads Our
More informationPlease note that these comments and the identity of the sender will be published unless a specific justified objection is received.
30 July 2016 Submission of comments on 'Draft guideline on the clinical investigation of medicines for the treatment of Alzheimer s disease and other dementias ' (EMA/CHMP/539931/2014) Comments from: Name
More informationPapers. Cholinesterase inhibitors for patients with Alzheimer s disease: systematic review of randomised clinical trials. Abstract. Methods.
Cholinesterase inhibitors for patients with Alzheimer s disease: systematic review of randomised clinical trials Abstract Objectives Pharmacological treatment of Alzheimer s disease focuses on correcting
More informationClinicopathologic and genetic aspects of hippocampal sclerosis. Dennis W. Dickson, MD Mayo Clinic, Jacksonville, Florida USA
Clinicopathologic and genetic aspects of hippocampal sclerosis Dennis W. Dickson, MD Mayo Clinic, Jacksonville, Florida USA The hippocampus in health & disease A major structure of the medial temporal
More informationCharacterizing Anatomical Variability And Alzheimer s Disease Related Cortical Thinning in the Medial Temporal Lobe
Characterizing Anatomical Variability And Alzheimer s Disease Related Cortical Thinning in the Medial Temporal Lobe Long Xie, Laura Wisse, Sandhitsu Das, Ranjit Ittyerah, Jiancong Wang, David Wolk, Paul
More informationMR Imaging of the Hippocampus in Normal Pressure Hydrocephalus: Correlations with Cortical Alzheimer s Disease Confirmed by Pathologic Analysis
AJNR Am J Neuroradiol 21:409 414, February 2000 MR Imaging of the Hippocampus in Normal Pressure Hydrocephalus: Correlations with Cortical Alzheimer s Disease Confirmed by Pathologic Analysis Sakari Savolainen,
More informationDetection of Mild Cognitive Impairment using Image Differences and Clinical Features
Detection of Mild Cognitive Impairment using Image Differences and Clinical Features L I N L I S C H O O L O F C O M P U T I N G C L E M S O N U N I V E R S I T Y Copyright notice Many of the images in
More information