Serotoninergic Polymorphisms (5-HTTLPR and 5-HT2A): Association Studies with Psychosis in Alzheimer Disease
|
|
- Clinton Scott
- 6 years ago
- Views:
Transcription
1 GENETIC TESTING Volume 7, Number 4, 2003 Mary Ann Liebert, Inc. Serotoninergic Polymorphisms (5-HTTLPR and 5-HT2A): Association Studies with Psychosis in Alzheimer Disease A. ROCCHI, D. MICHELI, R. CERAVOLO, M.L. MANCA, G. TOGNONI, G. SICILIANO, and L. MURRI ABSTRACT Patients with Alzheimer disease (AD) often exhibit psychotic symptoms associated with cognitive impairment. A few association studies have been carried out to determine if the serotonin transporter and receptor genes are potential risk factors for AD and/or associated psychopathology. The aim of this study was to investigate the association of a serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the 5-HT2A receptor T102C polymorphism with the risk of developing dementia and/or psychotic symptoms in a group of sporadic AD patients from Italy. No significant differences in the distribution of allele and genotype frequencies of 5-HTTLPR and 5-HT2A T102C were found between patient and control groups. However, a significant association between the C102/C102 5-HT2A genotype and psychotic symptoms (p, 0.001) was observed. Our data strongly confirm results from previous studies suggesting that the C102 allele of the 5-HT2A receptor is associated with the occurrence of psychotic symptoms in AD. On the contrary, the serotonin transporter does not appear to be a major susceptibility factor in the pathophysiology of the disease. INTRODUCTION ALZHEIMER DISEASE (AD) is often complicated by psychiatric symptoms, which occur in one-third of patients at an early stage of the disease (Burns et al., 1990a,b; Ballard et al., 1999; Paulsen et al., 2000). The possible hypotheses for psycho-pathology in AD involve selective loss of different neuronal populations, alterations of specific neurotransmitter systems, and genetic risk factors (Forstl et al., 1994; Holmes et al., Blusztajn and Berse, 2000). Serotonin (5-hydroxytryptamine, 5-HT) is a key neurotransmitter involved in the control of mood and a variety of traits and behaviors. Serotonin dysfunction has been implicated in the pathogenesis of many psychiatric diseases such as depression, obsessive-compulsive disorder, schizophrenia, and in the psychotic symptoms of patients diagnosed as having AD (Meltzer et al., 1998; Cross, 1990). Postmortem and biopsy studies of brains from patients with AD showed a decrease in the levels of 5-HT, of 5-HT receptors, and of the 5-HT transporter (5- HTT) sites (Bowen et al., 1983; Cheng et al., 1991; Tejani-Butt et al., 1995). In the 59 promoter region of the 5-HTT gene (chromosomal location 17q11.1 q12), there is an insertion/deletion polymorphism of one or more units of a base pair repeat, known as 5-HTTLPR (Lesch et al., 1994), which is the site of origin of a number of different alleles. The most common alleles are named long (L) and short (S), and they are characterized by a differential rate of transcription, with the long allele being more efficient (Collier et al., 1996; Heils et al., 1996). Recently, an allelic association between the 5-HTTLPR polymorphism and late-onset AD has been reported, but other authors did not confirm these data (Li et al., 1997; Oliveira et al., 1998; Hu et al., 2000; Zill et al., 2000). In the human 5-HT2A receptor gene, localized on chromosome 13q14 q21 (Sparkes et al., 1991), a single-nucleotide polymorphism (SNP) derived from a silent mutation is present at position 102 (T102C). Recent observations (Holmes et al., 1998; Nacmias et al., 2001) indicate that this and other common genetic polymorphisms in the 5-HT2A and 5-HT2C receptor genes may be risk factors for psychotic symptoms in the course of AD. Several studies investigated the association between apolipoprotein E (ApoE) genotype and psychotic symptoms in AD, but only inconclusive results were reported (Ramachandran et al., 1996; Harwood et al., 1999). In light of these considerations, we analyzed the distribution of the polymorphisms in the 5-HTT gene promoter region, 5- HT2A receptor, and ApoE genes in Italian patients with spo- Department of Neuroscience Neurological Clinics, University of Pisa, Pisa, Italy. 309
2 310 ROCCHI ET AL. TABLE 1. GENOTYPE DISTRIBUTION AND ALLELIC FREQUENCIES OF THE 5-HT2A T102C POLYMORPHISM IN AD AND CONTROL GROUPS Allele frequencies Groups n CC (%) TC (%) TT (%) C (%) T (%) AD (27.0) 64 (47.0) 35 (26.0) 136 (50.37) 134 (49.63) Controls (24.4) 40 (44.4) 28 (31.1) 84 (47.0)0 96 (53.0)0 radic AD, to obtain more information about their possible roles as AD risk factors and/or genetic determinants of predisposition to the development of AD-associated psychopathology. This is the first association study about 5-HTT and AD performed in an Italian population sample. The 5-HT2A receptor polymorphism has already been analyzed in Italy (Nacmias et al., 2001), but independently from the serotonin transporter. Our study will make possible a more comprehensive view of the involvement of the serotonin transmitter system in the pathophysiology of AD. Patients MATERIALS AND METHODS A total of 135 consecutive AD patients (90 females and 45 males, mean age at onset and SD: years) presenting to the University of Pisa, Alzheimer Disease Centre, Department of Neurosciences, were recruited. The diagnosis of probable AD was made according to DSM-IV and NINCDS-ADRDA criteria (McKhann et al., 1984). Cognitive assessment was made by means of a Mini-Mental State Examination (MMSE) and a complete neuropsychological battery, including reasoning, language, short- and long-term memory, and sustained and divided attention tasks. The Clinical Dementia Rating Scale and Instrumental Activities of Daily Living Scale were also performed to assess the functional ability of each AD patient. Behavioral assessment was carried on by means of the Neuropsychiatric Inventory (NPI), which is a care-giver-based instrument that evaluates 10 troublesome behaviors in patients with dementia. The 10 domains assessed by using the NPI are delusions, hallucinations, agitation, depression, anxiety, euphoria, apathy, disinhibition, irritability, and abnormal motor output. The cognitive evaluation and NPI were administered at the same time. Each patient or, when requested, his legal guardian gave an informed written consent to carry on the study. As controls, we studied a group of 90 age- and sex-matched non-demented individuals (mean age and SD: years). All control subjects were evaluated to exclude the concomitant finding of other neurological or psychiatric disorders. DNA analysis Genomic DNA was extracted from peripheral blood lymphocytes, according to standard procedures (Maniatis et al., 1982). 5-HT2A T102C and 5-HTTLPR polymorphisms were typed by a method involving polymerase chain reaction (PCR) amplification. The amplification of 5-HT2A T102C was followed by Msp I digestion (Holmes et al., 1998). PCR conditions for typing 5-HTTLPR were performed according to Collier and co-workers (Collier et al., 1996). This protocol is engineered to discriminate only between the two most common alleles (L or S). The various genotypes were detected on a 3.5% metaphor-agarose gel after electrophoresis. The ApoE genotypes were detected using the oligonucleotide primers 59-TCGGCCGCAGGGCGCTGATGG-3 9 and 59- TCGCGGGCCCCGGCCTGGTA-3 9. PCR amplification was performed by using 25 ng of genomic DNA, 0.1 mm of each primer and 1.5 mm MgCl 2 in a final volume of 20 ml. The sample was subjected to one cycle of 2 min at 95 C, then 30 cycles of 30 sec duration at 90 C, 30 sec at 67 C, 30 sec at 72 C, and finally 72 C for 7 min. The PCR product was digested using the enzyme Hha I. The frequency of ApoE alleles was compared with epidemiological data from the literature (Mayeux et al., 1998). Statistical analysis Comparison of genotype distributions and allele frequencies between patients and controls were evaluated by x 2 statistics. In all tests, a significance level of p, 0.05 was required. TABLE 2. GENOTYPE DISTRIBUTION AND ALLELIC FREQUENCIES OF THE 5-HT2A T102C POLYMORPHISM IN AD CASES WITH PSYCHOSIS AND WITHOUT PSYCHOSIS Allele frequencies Groups n CC (%) TC (%) TT (%) C (%) T (%) AD with (44.8) 24 (41.4) 8 (13.8) 77 (66.0) 41 (34.0) psychosis AD without (13.0) 40 (51.9) 27 (35.1) 59 (39.0) 93 (61.0) pychosis Total (27.0) 64 (47.0) 35 (26.0) 136 (50.37) 134 (49.63)
3 SEROTONINERGIC POLYMORPHISMS IN AD 311 TABLE 3. GENOTYPE DISTRIBUTION AND ALLELE FREQUENCIES OF THE 5-HT2A T102C POLYMORPHISM IN AD PATIENTS WITH AND WITHOUT PSYCHOTIC SYMPTOMS AFTER STRATIFICATION ACCORDING TO THE PRESENCE OR ABSENCE OF APOE «4 ALLELE AD with psychosis AD without psychosis ApoE«41 ApoE«42 ApoE«41 ApoE«42 n 5 26 n 5 32 n 5 26 n 5 51 TT (%) 3 (11.5) 5 (15.6) 10 (38.5) 16 (31.4) TC (%) 11 (42.3) 13 (40.6) 12 (46.2) 29 (56.8) CC (%) 12 (46.2) 14 (43.8) 4 (15.4) 6 (11.8) Alleles T (%) 17 (32.7) 23 (35.9) 32 (61.5) 61 (59.8) C (%) 35 (67.3) 41 (64.1) 20 (38.5) 41 (40.2) RESULTS Clinical features of patients On the basis of the NPI assessment, AD patients were divided into two subgroups: patients with psychotic symptoms (n 5 58, 43%) and without psychotic symptoms (n 5 77, 57%). In more detail, all psychotic patients had delusions and half had hallucinations. The most common delusions were of burglary and infidelity, whereas visual hallucinations were more prevalent than auditory ones. Trends for lower MMSE (p ), greater agitation (p ), and anxiety (p ), with lower aberrant motor behavior (p ) were present in the psychotic group with respect to the nonpsychotic group. No significant difference was observed between the two subgroups (psychotic vs. nonpsychotic patients) in terms of duration of the disease ( years, vs years). Also, no difference was reported between psychotic and nonpsychotic AD patients regarding severity of the dementia and functional ability in daily living, as assessed by Clinical Dementia Rating and Instrumental Activity of Daily Living Scale. At the time of genetic testing, AD psychotic patients were taking the following neuroleptic drugs: 22 subjects, olanzapine; 18, risperidone; 5, clozapine. Thirteen patients were not in therapy because their behavioral disorder was newly diagnosed at the time of the examination. Of the AD patients, 125 out of all 135 included in the study were taking for cognitive pharmacological support, cholinesterase inhibitors at optimal doses (54, rivastigmine; 10, galantamine; 61, donepezil). In the clinical follow-up at 2 years, as expected, AD psychotic patients exhibited an accelerated cognitive decline, when compared to AD non-psychotic patients. 5-HT2A T102C polymorphism Table 1 shows the genotype distribution and allele frequencies of the 5-HT2A T102C polymorphism in cases and controls. The genotype and allele distributions of sporadic AD cases did not deviate from the Hardy-Weinberg equilibrium and were comparable to controls. On the contrary, when we considered the presence or not of psychotic symptoms, the allele and genotype frequencies differed significantly between AD patients with and without psychiatric features (x , p, 0.001). For AD subjects with psychosis, 44.8% were homozygous for the C102 allele, compared to 13% of AD without psychosis (Table 2), indicating a segregation of the CC genotype with psychotic symptoms, whereas the TT genotype was associated with absence of psychosis (35.1% vs. 13.8%). In terms of allelic frequency, the C allele was overrepresented in the AD group with psychosis (66%); conversely, in patients without psychosis, there was a higher frequency of the T allele (61%). A stratification of the 5-HT2A data based on the presence or absence of the ApoE «4 allele (patients with one or more «4 alleles were considered as «41 and the others as «42) did not show any association between ApoE genotypes and the presence of psychotic symptoms, or between ApoE and 5-HT2A genotypes (Table 3). TABLE 4. GENOTYPE DISTRIBUTION AND ALLELE FREQUENCIES OF THE 5-HTTLPR POLYMORPHISM IN AD PATIENTS, WITH AND WITHOUT PSYCHOTIC SYMPTOMS, AND CONTROLS Genotype Allele frequencies Group n SS (%) LS (%) LL (%) S (%) L (%) AD cases (23.0) 54 (40.0) 50 (37.0) 116 (43.0) 154 (57.0) AD with (18.9) 28 (48.3) 19 (32.8) 50 (43.0) 66 (57.0) psychosis AD without (26.0) 26 (33.8) 31 (40.2) 66 (43.0) 88 (57.0) psychosis Controls (23.3) 38 (42.2) 31 (34.5) 80 (44.0) 100 (56.0)
4 312 ROCCHI ET AL. TABLE 5. GENOTYPE DISTRIBUTION AND ALLELE FREQUENCIES OF THE 5-HTTLPR POLYMORPHISM IN AD PATIENTS WITH AND WITHOUT PSYCHOTIC SYMPTOMS, AFTER STRATIFICATION OF PATIENTS INTO APOE«41 AND APOE«42 GROUPS AD with psychosis AD without psychosis ApoE«41 ApoE«42 ApoE«41 ApoE«42 n 5 26 n 5 32 n 5 26 n 5 51 LL (%) 9 (34.6) 9 (28.1) 10 (38.5) 21 (41.2) LS (%) 12 (46.2) 18 (56.3) 8 (30.8) 18 (35.3) SS (%) 5 (19.2) 5 (15.6) 8 (30.8) 12 (23.5) Alleles f (L) 58% 56% 54% 59% f (S) 42% 44% 46% 41% 5-HTTLPR polymorphism Table 4 shows the genotype distribution and allele frequencies of the 5-HTTLPR polymorphism in cases and controls. The genotype and allele distributions of sporadic AD cases did not deviate from the Hardy-Weinberg equilibrium and were comparable to controls. Table 4 also displays the genotype and allele frequencies of 5-HTTLPR in the two subgroups of AD patients with and without psychosis: No correlation was present between psychotic symptoms and 5-HTTLPR. To assess a possible association between 5-HTT and ApoE polymorphism, patients were grouped according to the presence (ApoE «41) or absence (ApoE «42) of the «4 allele. No differences could be detected between carriers and noncarriers of the «4 allele in the frequency distribution of alleles and genotypes of the 5-HTT polymorphism, both in psychotic and nonpsychotic patients (Table 5). ApoE polymorphism Allelic and genotype frequency distributions of the ApoE polymorphism in our sample are in Hardy-Weinberg equilibrium, and, as shown in Table 6, confirm the results obtained in the numerous studies about the association between AD and ApoE: There is a highly significant difference in the genotype and allele frequencies of the ApoE «4 polymorphism between patients and controls (x , p, 0.001). DISCUSSION The T102C polymorphism in the 5-HT2A gene has been previously considered a susceptibility factor for the development of schizophrenia, bipolar affective disorders, and eating disorders (Williams et al., 1996; Collier et al., 1997; Sorbi et al., 1998). Moreover, a significant loss of 5-HT2A receptors was reported in postmortem and in vivo studies on AD patients with behavioral alterations (Cross et al., 1986; Blin et al., 1993). Results from our study strongly confirm that genetic variation at the 5-HT2A gene locus is associated with the development of psychotic symptoms in AD and, with regard to this, the C102 allele might play a significant role in the clinical course of the disease. The finding of such a positive association points to this genotype as a risk factor for the occurrence of psychosis in AD. Because the T102C polymorphism does not cause a change in the 5-HT2A amino acid sequence, our results may be the consequence of the existence of a functional polymorphism elsewhere in the gene, which could be in linkage disequilibrium with the T102C variation. Actually, as reported in a paper by Arranz et al. (1998a), the T102C polymorphism has been shown to be in linkage disequilibrium with the G/A promoter polymorphism of the same gene, which would affect the expression levels of the receptor protein. Association studies of the serotonin transporter gene in AD and related psychopathology have yielded conflicting results (Kunugi et al., 2000; Zill et al., 2000; Sukonick et al., 2001; Tsai, 2001). Our data confirm that there was no association between 5-HTTLPR and psychotic symptoms in AD, suggesting that the genetic variation at the 5-HTT locus does not constitute a susceptibility factor for either AD risk or the development of psychotic symptoms in AD patients. Our data fail to detect any synergistic effect between ApoE and polymorphisms of the serotoninergic system on the risk for AD. This is because the genotypic distributions of the 5- HTTLPR and 5-HT2A polymorphisms are not significantly different between carriers and noncarriers of the ApoE «4 allele, both in the AD and control groups. However, in accordance with previous studies, in our population sample, the «4 allele TABLE 6. GENOTYPE DISTRIBUTION AND ALLELIC FREQUENCIES OF THE APOE POLYMORPHISM IN AD PATIENTS AND CONTROLS AD Controls n n 5 90 E2E2 0 0 E2E3 2 4 E2E4 1 0 E3E E3E E4E Sum Alleles (%) E2 1.1% 2.3% E3 75.6% 94.3% E4 23.3% 3.4%
5 SEROTONINERGIC POLYMORPHISMS IN AD 313 was found to be the major determinant of susceptibility to sporadic late-onset AD. Several studies analyzed the association between psychotic symptoms and the presence of the ApoE «4 allele (Forsell et al., 1998; Levy et al., 1999). Earlier work reported an increase of the «4 frequency in psychotic patients (Ramachandran et al., 1996); however, later work did not find a positive association (Harwood et al., 1999). In the present study, we failed to detect any association between a particular genotype in 5-HT2A or 5-HTT and the presence or absence of the «4 allele in patients stratified according to a clinical diagnosis of psychosis. Therefore, we have to conclude that ApoE is not a key factor in the development of psychotic symptoms during the course of AD. In conclusion, these rather common polymorphisms of genes of the serotoninergic system are not involved in the basic mechanisms of AD pathogenesis, but 5-HT2A seems to act like a genetic risk factor for the development of psychotic symptoms in those with AD. This datum can be significant in light of recent studies on schizophrenic patients (Arranz et al., 1998a,b) showing an association between the T102C and two other polymorphisms in the 5-HT2A gene and response to clozapine, an atypical antipsychotic drug with affinity for serotonin receptor binding sites. The C102 homozygous genotype was more frequent in patients who were clozapine-resistant than in patients who were responsive. In summary, this study shows that in patients with sporadic AD, psychotic symptoms are strongly associated with the C102 allele of the 5-HT2A gene and supports the usefulness of genetic screening in the search for determinant factors of noncognitive symptomatology in AD. Our finding may provide a tool to identify those patients who would benefit from the early introduction of antipsychotic therapy. REFERENCES ARRANZ, M.J., MUNRO, J., OWEN, M.J., SPURLOCK, G., SHAM, P., ZHAO, J., KIROV, G., COLLIER, D.A., and KERWIN, R.W. (1998a). Evidence for association between polymorphisms in the promoter and coding regions of the 5-HT2A receptor gene and response to clozapine. Mol. Psychiatr. 3, ARRANZ, M.J., MUNRO, J., SHAM, P., KIROV, G., MURRAY, R.M., COLLIER, D.A., and KERWIN, R.W. (1998b). Meta-analysis of studies on genetic variation in 5-HT2A receptors and clozapine response. Schizophr. Res. 32, BALLARD, C., GRAY, A., and AYRE, G. (1999). Psychotic symptoms, aggression and restlessness in dementia. Rev. Neurol. 155, BLIN, J., BARON, J.C., DUBOIS, B., CROUZEL, C., FIORELLI, M., ATTAR-LEVY, D., PILLON, B., FOURNIER, D., VIDAILHET, M., and AGID, Y. (1993). Loss of brain 5-HT2 receptors in Alzheimer s disease. In vivo assessment with positron emission tomography and [18F]setoperone. Brain 116(Pt 3), BLUSZTAJN, J.K., and BERSE, B. (2000). The cholinergic neuronal phenotype in Alzheimer s disease. Metab. Brain Dis. 15, BOWEN, D.M., ALLEN, S.J., BENTON, J.S., et al. (1983). Biochemical assessment of serotonergic and cholinergic dysfunction and cerebral atrophy in Alzheimer s disease. J. Neurochem. 41, BURNS, A., JACOBY, R., and LEVY, R. (1990a). Psychiatric phenomena in Alzheimer s disease. I: Disorders of thought content. Br. J. Psychiatr. 157, BURNS, A., JACOBY, R., and LEVY, R. (1990b). Psychiatric phenomena in Alzheimer s disease. II: Disorders of perception. Br. J. Psychiatr. 157, CHENG, A.V., FERRIER, I.N., MORRIS, C.M., JABEEN, S., SAH- GAL, A., MCKEITH, I.G., EDWARDSON, J.A., PERRY, R.H., and PERRY, E.K. (1991). Cortical serotonin-s2 receptor binding in Lewy body dementia, Alzheimer s and Parkinson s diseases. J. Neurol. Sci. 106, COLLIER, D.A., STOBER, G., LI, T., HEILS, A., CATALANO, M., DI BELLA, D., ARRANZ, M.I., MURRAY, R.M., VALLADA, H.P., BENGEL, D., MULLER, C.R., ROBERTS, G.W., SMERALDI, E., KIROV, G., SHAM, P., and LESCH, K.P. (1996). A novel functional polymorphism within the promoter of the serotonin transporter gene: possible role in susceptibility to affective disorders. Mol. Psychiatr. 6, COLLIER, D.A., ARRANZ, M.J., LI, T., MUPITA, D., BROWN, N., and TREASURE, J. (1997). Association between 5-HT2A gene promoter polymorphism and anorexia nervosa. Lancet 350, 412. CROSS, A.J. (1990). Serotonin in Alzheimer-type dementia and other dementing illnesses. Ann. N.Y. Acad. Sci. 600, CROSS, A.J., CROW, T.J., FERRIER, I.N., and JOHNSON, J.A. (1986). The selectivity of the reduction of serotonin S2 receptors in Alzheimer-type dementia. Neurobiol. Aging 7, 3 7. FORSELL, Y., BASUN, H., CORDER, E.H., LANNFELT, L., and WINBLAD, B. (1998). Psychotic symptoms and apolipoprotein E genotypes in an elderly population. Biol. Psychiatr. 44, FORSTL, H., BURNS, A., LEVY, R., and CAIRNS, N. (1994). Neuropathological correlates of psychotic phenomena in confirmed Alzheimer s disease. Br. J. Psychiatr. 165, HARWOOD, D.G., BARKER, W.W., OWNBY, R.L., ST. GEORGE- HYSLOP, P., and DUARA, R. (1999). Apolipoprotein-E (APO-E) genotype and symptoms of psychosis in Alzheimer s disease. Am. J. Geriatr. Psychiatr. 7, HEILS, A., TEUFEL, A., PETRI, S., STOBER, G., RIEDERER, P., BENGEL, D., and LESCH, K.P. (1996). Allelic variation of human serotonin transporter gene expression. J. Neurochem. 66, HOLMES, C., ARRANZ, M.J., POWELL, J.F., COLLIER, D.A., and LOVESTONE, S. (1998). 5-HT2A and 5-HT2C receptor polymorphisms and psychopathology in late onset Alzheimer s disease. Hum. Mol. Genet. 7, HU, M., RETZ, W., BAADER, M., PESOLD, B., ADLER, G., HENN, F.A., ROSLER, M., and THOME, J. (2000). Promoter polymorphism of the 5-HT transporter and Alzheimer s disease. Neurosci. Lett. 294, KUNUGI, H., UEKI, A., OTSUKA, M., ISSE, K., HIRASAWA, H., KATO, N., NABIKA, T., KOBAYASHI, S., and NANKO, S. (2000). Alzheimer s disease and 5-HTTLPR polymorphism of the serotonin transporter gene: no evidence for an association. Am. J. Med. Genet. 96, LESCH, K.P., BALLING, U., GROSS, J., STRAUSS, K., WOLOZIN, B.L., MURPHY, D.L., and RIEDERER, P. (1994). Organization of the human serotonin transporter gene. J. Neural Transm. 95, LEVY, M.L., CUMMINGS, J.L., FAIRBANKS, L.A., SULTZER, D.L., and SMALL, G.W. (1999). Apolipoprotein E genotype and noncognitive symptoms in Alzheimer s disease. Biol. Psychiatr. 45, LI, T., HOLMES, C., SHAM, P.C., VALLADA, H., BIRKETT, J., KIROV, G., LESCH, K.P., POWELL, J., LOVESTONE, S., and COLLIER, D. (1997). Allelic functional variation of serotonin transporter expression is a susceptibility factor for late onset Alzheimer s disease. Neuroreport 8, MANIATIS, T., FRITSCH, E.F., and SAMBROOK, J. (1982). Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY. MAYEUX, R., SAUNDERS, A.M., SHEA, S., et al. (1998). Utility of
6 the apolipoprotein E genotype in the diagnosis of Alzheimer s disease. N. Engl. J. Med. 338, MCKHANN, G., DRACHMAN, D., FOLSTEIN, M., KATZMAN, R., PRICE, D., and STADLAN, E.M. (1984). Clinical diagnosis of Alzheimer s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer s Disease. Neurology 34, MELTZER, C.C., SMITH, G., DEKOSKY, S.T., POLLOCK, B.G., MATHIS, C.A., MOORE, R.Y., KUPFER, D.J., and REYNOLDS, C.F. (1998). Serotonin in aging, late-life depression, and Alzheimer s disease: the emerging role of functional imaging. Neuropsychopharmacology 6, NACMIAS, B., TEDDE, A., FORLEO, P., PIACENTINI, S., GUARNIERI, B.M., BARTOLI, A., ORTENZI, L., PETRUZZI, C., SERIO, A., MARCON, G., and SORBI, S. (2001). Association between 5-HT(2A) receptor polymorphism and psychotic symptoms in Alzheimer s disease. Biol. Psychiatr. 50, OLIVEIRA, J.R., GALLINDO, R.M., MAIA, L.G., BRITO-MAR- QUES, P.R., OTTO, P.A., PASSOS-BUENO, M.R., MORIAS, M.A., Jr., and ZATZ, M. (1998). The short variant of the polymorphism within the promoter region of the serotonin transporter gene is a risk factor for late onset Alzheimer s disease. Mol. Psychiatr. 3, PAULSEN, J.S., SALMON, D.P., THAL, L.J., ROMERO, R., WEIS- STEIN-JENKINS, C., GALASKO, D., HOFSTETTER, C.R., THOMAS, R., GRANT, I., and JESTE, D.V. (2000). Incidence of and risk factors for hallucinations and delusions in patients with probable AD. Neurology 54, RAMACHANDRAN, G., MARDER, K., TANG, M., SCHOFIELD, P.W., CHUN, M.R., DEVANAND, D.P., STERN, Y., and MAYEUX, R. (1996). A preliminary study of apolipoprotein E genotype and psychiatric manifestations of Alzheimer s disease. Neurology 47, SORBI, S., NACMIAS, B., TEDDE, A., RICCA, V., MEZZANI, B., and ROTELLA, C.M. (1998). 5-HT2A promoter polymorphism in anorexia nervosa. Lancet 351, ROCCHI ET AL. SPARKES, R.S., LAN, N., KLISAK, I., MOHANDAS, T., DIEP, A., KOJIS, T., HEINZMANN, C., and SHIH, J.C. (1991). Assignment of a serotonin 5-HT 2 receptor gene (HTR2) to human chromosome 13q14 q21 and mouse chromosome 14. Genomics 9, SUKONICK, D.L., POLLOCK, B.G., SWEET, R.A., MULSANT, B.H., ROSEN, J., KLUNK, W.E., KASTANGO, K.B., DEKOSKY, S.T., and FERRELL, R.E. (2001). The 5-HTTPR*S/*L polymorphism and aggressive behavior in Alzheimer disease. Arch. Neurol. 58, TEJANI-BUTT, S.M., YANG, J., and PAWLYK, A.C. (1995). Altered serotonin transporter sites in Alzheimer s disease raphe and hippocampus. Neuroreport 6, TSAI, S.J., HONG, C.J., LIU, T.Y., CHENG, C.Y., and LIU, H.C. (2001). Association study for a functional serotonin transporter gene polymorphism and late-onset Alzheimer s disease for Chinese patients. Neuropsychobiology 44, WILLIAMS, J., SPURLOCK, G., MCGUFFIN, P., MALLET, J., NOTHEN, M.M., GILL, M., ASCHAUER, H., NYLANDER, P.O., MACCIARDI, F., and OWEN, M.J. (1996). Association between schizophrenia and T102C polymorphism of the 5-hydroxytryptamine type 2a-receptor gene. Lancet 347, ZILL, P., PADBERG, F., DE JONGE, S., HAMPEL, H., BURGER, K., STUBNER, S., BOETSCH, T., JURGEN MOLLER, H., ACK- ENHEIL, M., and BONDY, B. (2000). Serotonin transporter (5-HTT) gene polymorphism in psychogeriatric patients. Neurosci. Lett. 284, Address reprint requests to: Dr. Anna Rocchi Department of Neuroscience Neurological Clinics Via Roma Pisa (I), Italy gsicilia@med.unipi.it
Polymorphic Variations in 5 HT2A, 5 HTT and DISC 1 in first episode schizophrenia patients
PolymorphicVariationsin5 HT2A,5 HTTandDISC1infirst episodeschizophreniapatients L.MedinaGonzález,DepartmentofClinicalChemistry,RamónyCajalHospital,Madrid. PhD.MJArranz,SectionofClinicalNeuropharmacologyattheInstituteofPsychiatry,
More informationORIGINAL CONTRIBUTION. Association of the Serotonin Transporter and Receptor Gene Polymorphisms in Neuropsychiatric Symptoms in Alzheimer Disease
ORIGINAL CONTRIBUTION Association of the Serotonin Transporter and Receptor Gene Polymorphisms in Neuropsychiatric Symptoms in Alzheimer Disease Frédéric Assal, MD; Maricela Alarcón, PhD; Esther C. Solomon,
More informationMolecular Neuroscience
Volume 27 Number 2, 2005 ISSN: 0895 8696 JOURNAL OF Molecular Neuroscience Editor-in-Chief: ILLANA GOZES, PhD In This Issue The Biological Clock Alzheimer s Immunization Signal Transduction/ Neuroprotection/
More informationLack of Association between Endoplasmic Reticulum Stress Response Genes and Suicidal Victims
Kobe J. Med. Sci., Vol. 53, No. 4, pp. 151-155, 2007 Lack of Association between Endoplasmic Reticulum Stress Response Genes and Suicidal Victims KAORU SAKURAI 1, NAOKI NISHIGUCHI 2, OSAMU SHIRAKAWA 2,
More informationDementia is a common neuropsychiatric disorder characterized by progressive impairment of
Focused Issue of This Month Diagnosis and Treatment for Behavioral and Psychological Symptoms of Dementia Byoung Hoon Oh, MD Department of Psychiatry, Yonsei University College of Medicine E - mail : drobh@yuhs.ac
More informationBEHAVIOURAL AND PSYCHOLOGICAL SYMPTOMS IN DEMENTIA
BEHAVIOURAL AND PSYCHOLOGICAL SYMPTOMS IN DEMENTIA Unmet needs What might be your behavioural response to this experience? Content Definition What are BPSD? Prevalence How common are they? Aetiological
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 informationHallucinations, delusions, and cognitive decline in Alzheimer s disease
172 Department of Neurological Sciences, Rush Alzheimer s Disease Center and Rush Institute for Healthy Aging, 1645 West Jackson Boulevard, Suite 675, Chicago, Illinois 60612, USA R S Wilson D W Gilley
More informationNeurocognitive Disorders Research to Emerging Therapies
Neurocognitive Disorders Research to Emerging Therapies Edward Huey, MD Assistant Professor of Psychiatry and Neurology The Taub Institute for Research on Alzheimer s Disease and the Aging Brain Columbia
More informationNEUROPSYCHOMETRIC TESTS
NEUROPSYCHOMETRIC TESTS CAMCOG It is the Cognitive section of Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) The measure assesses orientation, language, memory, praxis, attention, abstract
More informationNeuropsychiatric disturbances such as delusions,
Differential Neuropsychiatric Responses to Tacrine in Alzheimer s Disease: Relationship to Dementia Severity Daniel Kaufer, M.D. Jeffrey L. Cummings, M.D. Dianne Christine, R.N. Neuropsychiatric symptom
More informationBehavioral and Psychological Symptoms of Dementia: Part I Epidemiology, Neurobiology, Heritability, and Evaluation
Behavioral and Psychological Symptoms of Dementia: Part I Epidemiology, Neurobiology, Heritability, and Evaluation consultant360.com/print-version/15679 Introduction Behavioral and psychological symptoms
More informationPsychosis and Agitation in Dementia
Psychosis and Agitation in Dementia Dilip V. Jeste, MD Estelle & Edgar Levi Chair in Aging, Director, Stein Institute for Research on Aging, Distinguished Professor of Psychiatry & Neurosciences, University
More informationThe course of neuropsychiatric symptoms in dementia. Part II: relationships among behavioural sub-syndromes and the influence of clinical variables
INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY Int J Geriatr Psychiatry 2005; 20: 531 536. Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/gps.1317 The course of neuropsychiatric
More informationDEMENTIA and BPSD in PARKINSON'S DISEASE. DR. T. JOHNSON. NOVEMBER 2017.
DEMENTIA and BPSD in PARKINSON'S DISEASE. DR. T. JOHNSON. NOVEMBER 2017. Introduction. Parkinson's disease (PD) has been considered largely as a motor disorder. It has been increasingly recognized that
More informationPharmacological Treatment of Aggression in the Elderly
Pharmacological Treatment of Aggression in the Elderly Howard Fenn, MD Adjunct Clinical Associate Professor Department of Psychiatry and Behavioral Sciences Stanford University Self-Assessment Question
More informationPsychiatric Morbidity in Dementia Patients in a Neurology-Based Memory Clinic
Original Articles 179 Psychiatric Morbidity in Dementia Patients in a Neurology-Based Memory Clinic Ching-Sen Shih 1, Sui-Hing Yan 2, Ying-Hoo Ho 1, Yuh-Te Lin 1, Jie-Yuan Li 1, and Yuk-Keung Lo 1 Abstract-
More informationJordi Clarimón, PhD, Jaume Bertranpetit, PhD, Mercè Boada, PhD, MD, Lluís Tàrraga, BSc, and David Comas, PhD
ARTICLE HSP70-2 (HSPA1B) Is Associated With Noncognitive Symptoms in Late-Onset Alzheimer s Disease Jordi Clarimón, PhD, Jaume Bertranpetit, PhD, Mercè Boada, PhD, MD, Lluís Tàrraga, BSc, and David Comas,
More informationParkinsonian Disorders with Dementia
Parkinsonian Disorders with Dementia George Tadros Consultant in Old Age Liaison Psychiatry, RAID, Heartlands Hospital Professor of Dementia and Liaison Psychiatry, Aston Medical School Aston University
More informationManagement of the Acutely Agitated Long Term Care Patient
Management of the Acutely Agitated Long Term Care Patient 80 60 Graying of the Population US Population Over Age 65 Millions of Persons 40 20 0 1900 1920 1940 1960 1980 1990 2010 2030 Year Defining Dementia
More informationThe efficacy of Rivastigmine in the management of the behavioral and psychological symptoms of lewy body dementia- a review of literature
Review article: The efficacy of Rivastigmine in the management of the behavioral and psychological symptoms of lewy body dementia- a review of literature Dr. Ivan Netto 1, Aditya Iyer 2, Dr. Prathamesh
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 informationWorldwide, over 40 million people have. Pimavanserin in Alzheimer s Disease Psychosis: Efficacy in Patients with More Pronounced Psychotic Symptoms
The Journal of Prevention of Alzheimer s Disease - JPAD Volume 6, Number 1, 2019 Original Research The Author(s) Pimavanserin in Alzheimer s Disease Psychosis: Efficacy in Patients with More Pronounced
More informationNeuropsychiatric Manifestations in Vascular Cognitive Impairment Patients with and without Dementia
86 Neuropsychiatric Manifestations in Vascular Cognitive Impairment Patients with and without Dementia Pai-Yi Chiu 1,3, Chung-Hsiang Liu 2, and Chon-Haw Tsai 2 Abstract- Background: Neuropsychiatric profile
More informationWorldwide, over 40 million people have. Pimavanserin in Alzheimer s Disease Psychosis: Efficacy in Patients with More Pronounced Psychotic Symptoms
The Journal of Prevention of Alzheimer s Disease - JPAD Volume 6, Number 1, 2019 Original Research The Author(s) Pimavanserin in Alzheimer s Disease Psychosis: Efficacy in Patients with More Pronounced
More informationRange of neuropsychiatric disturbances in patients with Parkinson s disease
492 Section of Geriatric Psychiatry, Rogaland Psychiatric Hospital D Aarsland N G Lim C Janvin Department of Neurology, Central Hospital of Rogaland, Stavanger, Norway J P Larsen K Karlsen E Tandberg Departments
More informationA prospective study of dementia with Lewy bodies
Age and Ageing 998; 27: 6-66 998, British Geriatrics Society A prospective study of dementia with Lewy bodies CLIVE G. BALLARD, JOHN O'BRIEN, KATH LOWERX GARETH A. AYRE, RICHARD HARRISON, ROBERT PERRY,
More informationManagement of Agitation in Dementia. Kimberly Triplett Ferguson, MS4
Management of Agitation in Dementia Kimberly Triplett Ferguson, MS4 Objectives 1. Review recommended evaluation of agitated patients with dementia. 2. Discuss evidence concerning nonpharmacologic management.
More informationResearch Article Sex Differences in Neuropsychiatric Symptoms of Alzheimer s Disease: The Modifying Effect of Apolipoprotein E ε4 Status
Behavioural Neurology Volume 2015, Article ID 275256, 6 pages http://dx.doi.org/10.1155/2015/275256 Research Article Sex Differences in Neuropsychiatric Symptoms of Alzheimer s Disease: The Modifying Effect
More informationORIGINAL CONTRIBUTION. An Investigation of Clinical Correlates of Lewy Bodies in Autopsy-Proven Alzheimer Disease
ORIGINAL CONTRIBUTION An Investigation of Clinical Correlates of Lewy Bodies in Autopsy-Proven Alzheimer Disease Yaakov Stern, PhD; Diane Jacobs, PhD; James Goldman, MD; Estrella Gomez-Tortosa, PhD; Bradley
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 informationScreening and Management of Behavioral and Psychiatric Symptoms Associated with Dementia
Screening and Management of Behavioral and Psychiatric Symptoms Associated with Dementia Measure Description Percentage of patients with dementia for whom there was a documented screening* for behavioral
More informationPsychiatric and Behavioral Symptoms in Alzheimer s and Other Dementias. Aaron H. Kaufman, MD
Psychiatric and Behavioral Symptoms in Alzheimer s and Other Dementias Aaron H. Kaufman, MD Psychiatric and Behavioral Symptoms in Alzheimer s and Other Dementias Aaron H. Kaufman, M.D. Health Sciences
More informationBehavioral and Psychologic Symptoms in Different Types of Dementia
ORIGINAL ARTICLE Behavioral and Psychologic Symptoms in Different Types of Dementia Ming-Jang Chiu,* Ta-Fu Chen, Ping-Keung Yip, Mau-Sun Hua, 1 Li-Yu Tang 2 Background/Purpose: Behavioral and psychologic
More informationA functional serotonin transporter (5-HTT) polymorphism is associated with psychosis in neuroleptic-free schizophrenics
Molecular Psychiatry (1998) 3, 328 332 1998 Stockton Press All rights reserved 1359 4184/98 $12.00 ORIGINAL RESEARCH ARTICLE A functional serotonin transporter (5-HTT) polymorphism is associated with psychosis
More informationORIGINAL CONTRIBUTION. Delusions and Hallucinations Are Associated With Worse Outcome in Alzheimer Disease
ORIGINAL CONTRIBUTION Delusions and Hallucinations Are Associated With Worse Outcome in Alzheimer Disease Nikolaos Scarmeas, MD; Jason Brandt, PhD; Marilyn Albert, PhD; Georgios Hadjigeorgiou, MD; Alexandros
More informationPredictors of disease course in patients with probable Alzheimer's disease
Article abstract-the presence of extrapyramidal signs or psychosis may indicate greater disability in patients with probable Alzheimer's disease. We evaluated the ability of these signs, noted at a patient's
More informationThe Spectrum of Lewy Body Disease: Dementia with Lewy Bodies and Parkinson's Disease Dementia
Disclosures Research support, Parkinson Society Canada, Canadian Institutes of Health Research, Ministry of Economic Development and Innovation, Teva Novartis clinical trial, Principal Investigator CME
More informationBehavioral Aspects of Parkinson s Disease
Behavioral Aspects of Parkinson s Disease Joseph H. Friedman, MD Director, Movement Disorders Program Butler Hospital Dept of Neurology Alpert Medical School of Brown University 1 Disclosures Drugs will
More informationORIGINAL CONTRIBUTION. The Progression of Cognition, Psychiatric Symptoms, and Functional Abilities in Dementia With Lewy Bodies and Alzheimer Disease
ORIGINAL CONTRIBUTION The Progression of Cognition, Psychiatric Symptoms, and Functional Abilities in Dementia With Lewy Bodies and Alzheimer Disease Karina Stavitsky, BS; Adam M. Brickman, PhD; Nikolaos
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 informationAlzheimer's Disease An update on diagnostic criteria & Neuropsychiatric symptoms. l The diagnosis of AD l Neuropsychiatric symptoms l Place of the ICT
Alzheimer's Disease An update on diagnostic criteria & Neuropsychiatric symptoms State of the art lecture March 4-2012 Philippe H Robert, Philippe Nice - France Robert The diagnosis of AD Neuropsychiatric
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 informationORIGINAL CONTRIBUTION. Apolipoprotein E 4 and Age at Onset of Sporadic and Familial Alzheimer Disease in Caribbean Hispanics
ORIGINAL CONTRIBUTION Apolipoprotein E 4 and Age at Onset of Sporadic and Familial Alzheimer Disease in Caribbean Hispanics Lucia Olarte, BS; Nicole Schupf, PhD; Joseph H. Lee, DPH; Ming-Xin Tang, PhD;
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 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 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 informationAcetylcholinesterase inhibitors: donepezil, rivastigmine, tacrine or galantamine for non-alzheimer s dementia
STEER 2002; Vol 2: No.2 Acetylcholinesterase inhibitors: donepezil, rivastigmine, tacrine or galantamine for non-alzheimer s dementia Bunmi Fajemisin Evidence search date: November 2001 www.signpoststeer.org
More informationThe Brain-Derived Neurotrophic Factor Val66Met Polymorphism and Rate of Decline in Alzheimer s disease
Journal of Alzheimer s Disease 9 (2006) 43 49 43 IOS Press The Brain-Derived Neurotrophic Factor Val66Met Polymorphism and Rate of Decline in Alzheimer s disease Jenny Y-J Chuu, Joy L. Taylor, Jared Tinklenberg,
More informationClinical Characteristics of Behavioral and Psychological Symptoms in Patients with Drug-naïve Alzheimer s Disease
Dementia and Neurocognitive Disorders 2012; 11: 87-94 ORIGINAL ARTICLE Clinical Characteristics of Behavioral and Psychological Symptoms in Patients with Drug-naïve Alzheimer s Disease Yong Tae Kwak, M.D.,
More informationDEMENTIA WITH LEWY bodies (DLB) is the
Psychiatry and Clinical Neurosciences 2017; 71: 409 416 doi:10.1111/pcn.12511 Regular Article Association of premorbid personality with behavioral and psychological symptoms in dementia with Lewy bodies:
More informationALZHEIMER DISEASE (AD) AFfects
ORIGINAL CONTRIBUTION Executive Dysfunction in Alzheimer Disease Margaret M. Swanberg, DO; Rochelle E. Tractenberg, PhD, MPH; Richard Mohs, PhD; Leon J. Thal, MD; Jeffrey L. Cummings, MD Background: Executive
More informationThe Reliability and Validity of the Korean Instrumental Activities of Daily Living (K-IADL)
The Reliability and Validity of the Korean Instrumental Activities of Daily Living (K-IADL Sue J. Kang, M.S., Seong Hye Choi, M.D.*, Byung H. Lee, M.A., Jay C. Kwon, M.D., Duk L. Na, M.D., Seol-Heui Han
More informationThe place for treatments of associated neuropsychiatric and other symptoms
The place for treatments of associated neuropsychiatric and other symptoms Luca Pani dg@aifa.gov.it London, 25 th November 2014 Workshop on Alzheimer s Disease European Medicines Agency London, UK Public
More informationBehavioral and Psychological Symptoms of Dementia
Behavioral and Psychological Symptoms of Dementia Akarachaid Pinidbunjerdkool MD*, Sansanee Saengwanitch MD*, Pasiri Sithinamsuwan MD* * Division of Neurology, Department of Medicine, Phramongkutklao Hospital
More information5/2/18. After this class students should be able to: Stephanie Moon, Ph.D. - GWAS. How do we distinguish Mendelian from non-mendelian traits?
corebio II - genetics: WED 25 April 2018. 2018 Stephanie Moon, Ph.D. - GWAS After this class students should be able to: 1. Compare and contrast methods used to discover the genetic basis of traits or
More informationPredicting Lewy Body Pathology in a Community-Based Sample With Clinical Diagnosis of Alzheimer s Disease
Predicting Lewy Body Pathology in a Community-Based Sample With Clinical Diagnosis of Alzheimer s Disease Debby Tsuang, MD, MSc, Kate Simpson, MPH, Eric B. Larson, MD, MPH, Elaine Peskind, MD, Walter Kukull,
More informationWhite matter hyperintensities correlate with neuropsychiatric manifestations of Alzheimer s disease and frontotemporal lobar degeneration
White matter hyperintensities correlate with neuropsychiatric manifestations of Alzheimer s disease and frontotemporal lobar degeneration Annual Scientific Meeting Canadian Geriatric Society Philippe Desmarais,
More informationT he prevalence of Parkinson s disease (PD) is nearly 1% in
708 PAPER Donepezil for cognitive impairment in Parkinson s disease: a randomised controlled study D Aarsland, K Laake, J P Larsen, C Janvin... See end of article for authors affiliations... Correspondence
More informationSeverity and prevalence of behavioral and psychological symptoms among patients of different dementia stages in Taiwan
Original article Severity and prevalence of behavioral and psychological symptoms among patients of different dementia stages in Taiwan Si-Sheng Huang 1, Wen-Fu Wang 2, Yi-Cheng Liao 1 1 Department of
More informationPREVALENCE AND CORRELATES OF ANXIETY IN ALZHEIMER S DISEASE
166 Chemerinski et al. DEPRESSION AND ANXIETY 7:166 170 (1998) PREVALENCE AND CORRELATES OF ANXIETY IN ALZHEIMER S DISEASE Erán Chemerinski, M.D., 1 * Gustavo Petracca, M.D., 1 Facundo Manes, M.D., 2 Ramón
More informationThe Genetics of Major Depressive Disorder
The Genetics of Major Depressive Disorder Gin S. Malhi, MB, MRCPsych, Janette Moore, MB, MRCPsych, and Peter McGuffin, MB, PhD, FRCP, FRCPsych Address SGDP Research Centre, Institute of Psychiatry, DeCrespigny
More informationAssociation of PS1 1/2, ACE I/D, and LRP C/T polymorphisms with Alzheimer s disease in the Chinese population: a meta-analysis of case-control studies
Association of PS1 1/2, ACE I/D, and LRP C/T polymorphisms with Alzheimer s disease in the Chinese population: a meta-analysis of case-control studies L. Yang 1 *, H.-H. Zhou 1 *, Y.-F. Ye 1 *, X.-W. Fan
More informationORIGINAL ARTICLE. Early and Widespread Cholinergic Losses Differentiate Dementia With Lewy Bodies From Alzheimer Disease
ORIGINAL ARTICLE Early and Widespread Cholinergic Losses Differentiate Dementia With Lewy Bodies From Alzheimer Disease Pietro Tiraboschi, MD; Larry A. Hansen, MD; Michael Alford, BA; Annette Merdes, MD;
More informationValidity of Family History for the Diagnosis of Dementia Among Siblings of Patients With Late-onset Alzheimer s Disease
Genetic Epidemiology 15:215 223 (1998) Validity of Family History for the Diagnosis of Dementia Among Siblings of Patients With Late-onset Alzheimer s Disease G. Devi, 1,3 * K. Marder, 1,3 P.W. Schofield,
More informationComment on administration and scoring of the Neuropsychiatric Inventory in clinical trials
Alzheimer s & Dementia 4 (2008) 390 394 Comment on administration and scoring of the Neuropsychiatric Inventory in clinical trials Donald J. Connor a, *, Marwan N. Sabbagh a, Jeffery L. Cummings b a Cleo
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 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 informationPharmacological Treatments for Neuropsychiatric Symptoms in Dementia 3/22/2018
Pharmacological Treatments for Neuropsychiatric Symptoms in Dementia 3/22/2018 Mary Ellen Quiceno, MD, FAAN Associate Professor of Neurology UNTHSC Center for Geriatrics 855 Montgomery Street, PCC 4, Ft.
More informationAlzheimer disease (AD) is a devastating neurodegenerative
ORIGINAL ARTICLE Rates of Depression in Individuals With Pathologic But Not Clinical Alzheimer Disease are Lower Than Those in Individuals Without the Disease: Findings From the Baltimore Longitudinal
More informationAccelerated 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 informationVisual hallucinations in Alzheimer s disease is significantly associated with clinical diagnostic features of dementia with Lewy bodies
RESEARCH ARTICLE Visual hallucinations in Alzheimer s disease is significantly associated with clinical diagnostic features of dementia with Lewy bodies Pai-Yi Chiu 1, Min-Hsien Hsu 1, Chein-Wei Wang 2,
More informationAssociation between schizophrenia and DRD3 or HTR2 receptor gene variants
(2004) 12, 535 541 & 2004 Nature Publishing Group All rights reserved 1018-4813/04 $30.00 www.nature.com/ejhg ARTICLE Association between schizophrenia and DRD3 or HTR2 receptor gene variants S Baritaki
More informationReliability of the Brazilian Portuguese version of the Neuropsychiatric Inventory (NPI) for patients with Alzheimer s disease and their caregivers
International Psychogeriatrics (2008), 20:2, 383 393 C 2007 International Psychogeriatric Association doi:10.1017/s1041610207006254 Printed in the United Kingdom Reliability of the Brazilian Portuguese
More informationNIH Public Access Author Manuscript Metab Brain Dis. Author manuscript; available in PMC 2011 October 24.
NIH Public Access Author Manuscript Published in final edited form as: Metab Brain Dis. 2006 September ; 21(2-3): 235 240. doi:10.1007/s11011-006-9017-2. Risk factors for incident Alzheimer s disease in
More informationORIGINAL CONTRIBUTION. Attention and Fluctuating Attention in Patients With Dementia With Lewy Bodies and Alzheimer Disease
ORIGINAL CONTRIBUTION Attention and Fluctuating Attention in Patients With Dementia With Lewy Bodies and Alzheimer Disease Clive Ballard, MRCPsych, MD; John O Brien, MRCPsych, DM; Alistair Gray, BSc; Franchesca
More informationAllelic association between a Ser-9-Gly polymorphism in the dopamine D3 receptor gene and schizophrenia
Hum Genet (1996) 97 : 714 719 Springer-Verlag 1996 ORIGINAL INVESTIGATION Sanober Shaikh David A. Collier Pak C. Sham David Ball Katherine Aitchison Homero Vallada Iain Smith Michael Gill Robert W. Kerwin
More informationNATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE. Health Technology Appraisal
NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE Health Technology Appraisal Donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer's disease (Review of TA 111) Appraisal
More informationNEXT-Link DEMENTIA. A network of Danish memory clinics YOUR CLINICAL RESEARCH PARTNER WITHIN ALZHEIMER S DISEASE AND OTHER DEMENTIA DISEASES.
NEXT-Link DEMENTIA A network of Danish memory clinics YOUR CLINICAL RESEARCH PARTNER WITHIN ALZHEIMER S DISEASE AND OTHER DEMENTIA DISEASES. NEXT-Link DEMENTIA NEXT-Link DEMENTIA is a network of Danish
More informationCognitive Abilities Screening Instrument, Chinese Version 2.0 (CASI C-2.0): Administration and Clinical Application
Continuing Medical Education 180 Cognitive Abilities Screening Instrument, Chinese Version 2.0 (CASI C-2.0): Administration and Clinical Application Ker-Neng Lin 1,2, Pei-Ning Wang 1,3, Hsiu-Chih Liu 1,3,
More informationGenetic association between APOE*4 and neuropsychiatric symptoms in patients with probable Alzheimer's disease is dependent on the psychosis phenotype
Christie et al. Behavioral and Brain Functions 2012, 8:62 RESEARCH Open Access Genetic association between APOE*4 and neuropsychiatric symptoms in patients with probable Alzheimer's disease is dependent
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 informationResponsiveness of the QUALID to Improved Neuropsychiatric Symptoms in Patients with Alzheimer s Disease
ORIGINAL RESEARCH Responsiveness of the QUALID to Improved Neuropsychiatric Symptoms in Patients with Alzheimer s Disease Hadas Benhabib 1, Krista L. Lanctôt, PhD 1,2,4, Goran M. Eryavec, MD, FRCPC 3,4,
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 informationGERIATRIC MENTAL HEALTH AND MEDICATION TREATMENT
Psychiatry and Addictions Case Conference UW Medicine Psychiatry and Behavioral Sciences GERIATRIC MENTAL HEALTH AND MEDICATION TREATMENT RUTH KOHEN ASSOCIATE PROFESSOR UW DEPARTMENT OF PSYCHIATRY 5-4-2017
More informationMissing Data Analysis in Drug-Naïve Alzheimer s Disease with Behavioral and Psychological Symptoms
Original Article http://dx.doi.org/10.3349/ymj.2013.54.4.825 pissn: 0513-5796, eissn: 1976-2437 Yonsei Med J 54(4):825-831, 2013 Missing Data Analysis in Drug-Naïve Alzheimer s Disease with Behavioral
More informationN europsychiatric symptoms can induce marked disability
PAPER Neuropsychiatric profiles in patients with Alzheimer s disease and vascular dementia J-L Fuh, S-J Wang, J L Cummings... See end of article for authors affiliations... Correspondence to: Dr J-L Fuh,
More informationA Comparison of Family History of Psychiatric Disorders Among Patients With Early- and Late-Onset Alzheimer s Disease
A Comparison of Family History of Psychiatric Disorders Among Patients With Early- and Late-Onset Alzheimer s Disease Gayatri Devi, M.D. Jennifer Williamson, M.Sc. Fadi Massoud, M.D. Karen Anderson, M.D.
More informationDisclosure. Speaker Bureaus. Grant Support. Pfizer Forest Norvartis. Pan American Health Organization/WHO NIA HRSA
Disclosure Speaker Bureaus Pfizer Forest Norvartis Grant Support Pan American Health Organization/WHO NIA HRSA How Common is Psychosis in Alzheimer s Disease? Review of 55 studies 41% of those with Alzheimer
More informationImpact of cholinesterase inhibitors on behavioral and psychological symptoms of Alzheimer s disease: A meta-analysis
ORIGINAL RESEARCH Impact of cholinesterase inhibitors on behavioral and psychological symptoms of Alzheimer s disease: A meta-analysis Noll Campbell 1 Amir Ayub 2 Malaz A Boustani 2 Chris Fox 3 Martin
More information( delirium ) 15%- ( extrapyramidal syndrome ) risperidone olanzapine ( extrapyramidal side effect ) olanzapine ( Delirium Rating Scale, DRS )
2005 6 48-52 Olanzapine 30% ( delirium 5%- Haloperidol ( extrapyramidal syndrome risperidone ( extrapyramidal side effect ( Delirium Rating Scale, DRS ( Delirium ( Olanzapine ( Delirium Rating Scale, DRS
More informationBehavioural Problems and Patterns of Psychopharmacological Treatment given in Elderly Patients with Dementia
The International Journal of Indian Psychology ISSN 2348-5396 (e) ISSN: 2349-3429 (p) Volume 6, Issue 4, DIP: 18.01.090/20180604 DOI: 10.25215/0604.090 http://www.ijip.in October-December, 2018 Research
More informationThe human serotonin transporter gene linked polymorphism (5-HTTLPR) shows ten novel allelic variants
(2000) 5, 32 38 2000 Macmillan Publishers Ltd All rights reserved 1359-4184/00 $15.00 www.nature.com/mp IMMEDIATE COMMUNICATION The human serotonin transporter gene linked polymorphism (5-HTTLPR) shows
More informationNeuropsychiatric Symptoms of Patients With Progressive Supranuclear Palsy and Parkinson s Disease
Neuropsychiatric Symptoms of Patients With Progressive Supranuclear Palsy and Parkinson s Disease Dag Aarsland, M.D., Ph.D. Irene Litvan, M.D. Jan P. Larsen, M.D., Ph.D. Neuropsychiatric symptoms are common
More informationRoyal Free and University College Medical School, Department of Mental Health Sciences, University College London, London, England 2
PSYCHOGERIATRIA POLSKA 2004;1(3),175-184 artyku³ oryginalny original article The relationships between neuropsychiatric symptoms, cognitive deficit and prescription of psychotropics in Alzheimer s Disease:
More informationIndex. Note: Page numbers of article titles are in boldface type.
Index Note: Page numbers of article titles are in boldface type. A Abuse alcohol, aggression and, 52 53 substance, aggression and, 52 54 ACE. See Aid to Capacity Evaluation (ACE). AEDs. See Antiepileptic
More informationThey deserve personalized treatment
Your patients are unique They deserve personalized treatment New laboratory service offered by STA 2 R is a panel of genetic tests that gives prescribers answers to the clinical questions below. The test
More informationHydroxytryptamine transporter gene-linked polymorphic region (5HTTLPR) is associated with delusions in Alzheimer s disease
D Onofrio et al. Translational Neurodegeneration (2019) 8:4 https://doi.org/10.1186/s40035-019-0144-1 RESEARCH Open Access Hydroxytryptamine transporter gene-linked polymorphic region (5HTTLPR) is associated
More informationPDF hosted at the Radboud Repository of the Radboud University Nijmegen
PDF hosted at the Radboud Repository of the Radboud University Nijmegen The following full text is a preprint version which may differ from the publisher's version. For additional information about this
More information