Remember Me
Or use your Academic/Social account:


You have just completed your registration at OpenAire.

Before you can login to the site, you will need to activate your account. An e-mail will be sent to you with the proper instructions.


Please note that this site is currently undergoing Beta testing.
Any new content you create is not guaranteed to be present to the final version of the site upon release.

Thank you for your patience,
OpenAire Dev Team.

Close This Message


Verify Password:
Verify E-mail:
*All Fields Are Required.
Please Verify You Are Human:

OpenAIRE is about to release its new face with lots of new content and services.
During September, you may notice downtime in services, while some functionalities (e.g. user registration, login, validation, claiming) will be temporarily disabled.
We apologize for the inconvenience, please stay tuned!
For further information please contact helpdesk[at]openaire.eu

fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Hollingworth, Paul.
Languages: English
Types: Doctoral thesis
Subjects: RC0321
Late-onset Alzheimer's disease (LOAD) is a heritable disorder. It is invariably characterised by a decline in cognitive abilities, however, marked variation in behavioural symptoms and age at onset are observed between sufferers. This clinical heterogeneity may be genetically modified, hence, may provide a productive avenue of exploration for those seeking to unravel the genetic aetiology of LOAD. This thesis employed a sequential three stage approach to search for loci implicated in the development of genetically influenced features of the disease. Behavioural symptoms in 1,120 unrelated individuals with LOAD were assessed using the Neuropsychiatric Inventory. The 12 symptom domain scores were subjected to principal components analysis. Three interpretable components were identified, comprising: "frontal lobe dysfunction", "psychosis" and "mood". These components remained stable when taking account of disease severity. The familiality of clinical variation was assessed. Affected siblings from 388 families were characterised in terms of aggression, psychosis and mood disturbances. Age at onset data were available for affected siblings from 458 families. Familial clustering was found for age at onset, psychosis, aggression and mild depression, with the strongest evidence noted for age at onset and psychosis. Major depression and a combined phenotype of depression with anxiety showed limited evidence of familial aggregation. Covariate linkage analysis was employed to search for loci which may influence clinical variation in LOAD. This included a sample of 513 affected relative pairs. Increases in LOD were observed with age at onset (chromosome 1, 2,12,19 and 21), aggression (chromosome 9), psychosis (chromosome 7 and 15) and minor depression (chromosome 21). Understanding factors associated with behavioural symptoms and age at disease onset may lead to the achievable goal of disease modification. These findings support the hypothesis that clinical variation in AD is genetically modified, setting the stage for future linkage and association studies.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • 5. General discussion....................................................................... 180 5.1 Summary of findings.................................................................................180 5.2 Implications and future research............................................................ 183 5.3 Conclusions............................................................................................... 191
    • 4.1 Basic characteristicsof the family based samples used for linkage analysis.................................................. 151
    • 4.2 Pairwise symptom classifications among relative pairs in the UK, NIMH and combined sample..........................................................................152
    • 4.3 Summary of linkage results after including pairwise age at onset mean, difference and APOE.......................................................................... 153
    • 4.4 Variation in IBD and maximum LOD score with mean age at onset for chromosomes with significant mean age at onset effects..............................158
    • 4.5 Summary of linkage results after including psychosis and APOE...................159
    • 4.6 Summary of linkage results after including aggression and APOE.................164
    • 4.7 Summary of linkage results after including depression and APOE.................166 Farrer, L. A. et al. 1997. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. Jama 278(16), pp. 1349-1356.
    • Ferretti, L. et al. 2001. Anxiety and Alzheimer's disease. J Geriatr Psychiatry Neurol 14(1), pp. 52-58.
    • Fillenbaum, G. G. et al. 1998. The prevalence and 3-year incidence of dementia in older Black and White community residents. J Clin Epidemiol 51(7), pp. 587-595.
    • Finkel, S. I. 2001. Behavioral and psychological symptoms of dementia: a current focus for clinicians, researchers, and caregivers. J Clin Psychiatry 62 Suppl 21, pp. 3-6.
    • Fisfalen, M. E. et al. 2005. Familial variation in episode frequency in bipolar affective disorder. Am J Psychiatry 162(7), pp. 1266-1272.
    • Flynn, F. G. et al. 1991. Delusions in dementia syndromes: investigation of behavioral and neuropsychological correlates. J Neuropsychiatry Clin Neurosci 3(4), pp. 364-370.
    • Folstein, M. F. et al. 1975. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12(3), pp. 189-198.
    • Forsell, Y. et al. 1998. Psychotic symptoms and apolipoprotein E genotypes in an elderly population. Biol Psychiatry 44(2), pp. 139-140.
    • Fratiglioni, L. et al. 1993. Risk factors for late-onset Alzheimer's disease: a populationbased, case-control study. Ann Neurol 33(3), pp. 258-266.
    • Fratiglioni, L. et al. 1999. Worldwide prevalence and incidence of dementia. Drugs Aging 15(5), pp. 365-375.
    • Fratiglioni, L. et al. 1991. Prevalence of Alzheimer's disease and other dementias in an elderly urban population: relationship with age, sex, and education. Neurology 41(12), pp. 1886-1892.
    • Fratiglioni, L. et al. 1997. Very old women at highest risk of dementia and Alzheimer's disease: incidence data from the Kungsholmen Project, Stockholm. Neurology 48(1), pp. 132-138.
    • Freimer, N. and Sabatti, C. 2003. The human phenome project. Nat Genet 34(1), pp. 15- 21.
    • Frisoni, G. B. et al. 1999. Behavioral syndromes in Alzheimer's disease: description and correlates. Dement Geriatr Cogn Disord 10(2), pp. 130-138.
    • Frydman, M. et al. 1985. Assignment of the gene for Wilson disease to chromosome 13: linkage to the esterase D locus. Proc Natl Acad Sci U S A 82(6), pp. 1819-1821.
    • Fuh, J. L. et al. 2001. Behavioral disorders and caregivers' reaction in Taiwanese patients with Alzheimer's disease. Int Psychogeriatr 13(1), pp. 121-128.
    • Gabryelewicz, T. et al. 2002. Behavioural pathology in Alzheimer's disease with special reference to apolipoprotein E genotype. Dement Geriatr Cogn Disord 14(4), pp. 208-212.
    • Ganguli, M. et al. 2000. Ten-year incidence of dementia in a rural elderly US community population: the MoVIES Project. Neurology 54(5), pp. 1109-1116.
    • Garcia-Alloza, M. et al. 2005. Cholinergic-serotonergic imbalance contributes to cognitive and behavioral symptoms in Alzheimer's disease. Neuropsychologia 43(3), pp. 442-449.
    • Gatz, J. L. et al. 2005a. Do depressive symptoms predict Alzheimer's disease and dementia? J G erontol A B iol Sci M ed Sci 60(6), pp. 744-747.
    • Gatz, M. et al. 2005b. Complete ascertainment of dementia in the Swedish Twin Registry: the HARMONY study. N eurobiol Aging 26(4), pp. 439-447.
    • Gatz, M. et al. 1997. Heritability for Alzheimer's disease: the study of dementia in Swedish twins. J G erontol A B iol S ci M ed Sci 52(2), pp. M117-125.
    • Gaugler, J. E. et al. 2000. Predictors of institutionalization of cognitively impaired elders: family help and the timing of placement. J Gerontol B Psychol Sci Soc Sci 55(4), pp. P247-255.
    • Gaugler, J. E. et al. 1999. Caregiving and institutionalization: perceptions of family conflict and socioemotional support. I n tJ Aging Hum Dev 49(1), pp. 1-25.
    • Gauthier, S. et al. 2005. Effects of memantine on behavioural symptoms in Alzheimer's disease patients: an analysis of the Neuropsychiatric Inventory (NPI) data of two randomised, controlled studies. Int J G eriatr Psychiatry 20(5), pp. 459-464.
    • Gautrin, D. et al. 1990. Canadian projections of cases suffering from Alzheimer's disease and senile dementia of Alzheimer type over the period 1986-2031. Can J Psychiatry 35(2), pp. 162-165.
    • Gearing, M. et al. 1995. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part X. Neuropathology confirmation of the clinical diagnosis of Alzheimer's disease. N eurology 45(3 Pt 1), pp. 461-466.
    • Geser, F. et al. 2005. How to diagnose dementia with Lewy bodies: state of the art. Mov Disord 20 Suppl 12, pp. S11-20.
    • Ghebremedhin, E. et al. 2001. Gender and age modify the association between APOE and AD-related neuropathology. Neurology 56(12), pp. 1696-1701.
    • Ghosh, S. et al. 2000. The Finland-United States investigation of non-insulin-dependent diabetes mellitus genetics (FUSION) study. I. An autosomal genome scan for genes that predispose to type 2 diabetes. Am J Hum Genet 67(5), pp. 1174-1185.
    • Gillanders, E. M. et al. 2004. Combined genome-wide scan for prostate cancer susceptibility genes. J N atl C ancer Inst 96(16), pp. 1240-1247.
    • Glatt, S. J. et al. 2003. Association between a functional catechol O-methyltransferase gene polymorphism and schizophrenia: meta-analysis of case-control and familybased studies. A m J P sychiatry 160(3), pp. 469-476.
    • Goate, A. et al. 1991. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 349(6311), pp. 704-706.
    • Gomez-lsla, T. et al. 1996. Clinical and pathological correlates of apolipoprotein E epsilon 4 in Alzheimer's disease. Ann Neurol 39(1), pp. 62-70.
    • Gorwood, P. 2004. Generalized anxiety disorder and major depressive disorder comorbidity: an example of genetic pleiotropy? Eur Psychiatry 19(1), pp. 27-33.
    • Gottesman, II and Gould, T. D. 2003. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 160(4), pp. 636-645.
    • Greenwood, C. M. and Bull, S. B. 1997. Incorporation of covariates into genome scanning using sib-pair analysis in bipolar affective disorder. Genet Epidemiol 14(6), pp. 635-640.
    • Greenwood, C. M. and Bull, S. B. 1999. Analysis of affected sib pairs, with covariates-- with and without constraints. Am J Hum Genet 64(3), pp. 871-885.
    • Grossman, M. et al. 2004. What's in a name: voxel-based morphometric analyses of MRI and naming difficulty in Alzheimer's disease, frontotemporal dementia and corticobasal degeneration. Brain 127(Pt 3), pp. 628-649.
    • Guo, Z. et al. 1999. Occurrence and progression of dementia in a community population aged 75 years and older: relationship of antihypertensive medication use. Arch Neurol 56(8), pp. 991-996.
    • Gussekloo, J. et al. 1995. A community based study of the incidence of dementia in subjects aged 85 years and over. J Neurol Neurosurg Psychiatry 59(5), pp. 507- 510.
    • Gutierrez, B. et al. 1996. Allelic association analysis of the 5-HT2C receptor gene in bipolar affective disorder. Neurosci Lett 212(1), pp. 65-67.
    • Hachinski, V. C. et al. 1975. Cerebral blood flow in dementia. Arch Neurol 32(9), pp. 632- 637.
    • Hagnell, O. et al. 1992. Incidence of dementia in the Lundby Study. Neuroepidemiology 11 Suppl 1, pp. 61-66.
    • Hallmayer, J. F. et al. 2005. Genetic evidence for a distinct subtype of schizophrenia characterized by pervasive cognitive deficit. Am J Hum Genet 77(3), pp. 468-476.
    • Hamshere, M. L. et al. 2005. Genome-wide significant linkage in schizophrenia conditioning on occurrence of depressive episodes. J Med G enet
    • Harper, D. G. et al. 2005. Disturbance of endogenous circadian rhythm in aging and Alzheimer disease. Am J G eriatr Psychiatry 13(5), pp. 359-368.
    • Harwood, D. G. et al. 2000. Relationship of behavioral and psychological symptoms to cognitive impairment and functional status in Alzheimer's disease. Int J Geriatr Psychiatry 15(5), pp. 393-400.
    • Harwood, D. G. et al. 1999. Apolipoprotein-E (APO-E) genotype and symptoms of psychosis in Alzheimer's disease. Am J Geriatr Psychiatry 7(2), pp. 119-123.
    • Harwood, D. G. et al. 1998. The behavioral pathology in Alzheimer's Disease Scale (BEHAVE-AD): factor structure among community-dwelling Alzheimer's disease patients. In tJ G eriatr Psychiatry 13(11), pp. 793-800.
    • Haupt, M. et al. 1998. Presentation and stability of noncognitive symptom patterns in patients with Alzheimer disease. Alzheimer Dis Assoc Disord 12(4), pp. 323-329.
    • Haupt, M. et al. 1992. Alzheimer's disease: identical phenotype of familial and non-familial cases. J Neurol 239(5), pp. 248-250.
    • Hauser, E. R. et al. 2004. Ordered subset analysis in genetic linkage mapping of complex traits. Genet Epidem iol 27(1), pp. 53-63.
    • Havlik, R. J. et al. 2000. APOE-epsilon4 predicts incident AD in Japanese-American men: the honolulu-asia aging study. Neurology 54(7), pp. 1526-1529.
    • Hebert, L. E. et al. 1995. Age-specific incidence of Alzheimer's disease in a community population. Jama 273(17), pp. 1354-1359.
    • Hebert, L. E. et al. 2003. Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol 60(8), pp. 1119-1122.
    • Henderson, V. W. et al. 1989. Spatial disorientation in Alzheimer's disease. Arch Neurol 46(4), pp. 391-394.
    • Henderson, V. W. et al. 1994. Estrogen replacement therapy in older women. Comparisons between Alzheimer's disease cases and nondemented control subjects. Arch Neurol 51(9), pp. 896-900.
    • Hendrie, H. C. 1998. Epidemiology of dementia and Alzheimer's disease. Am J Geriatr Psychiatry 6(2 Suppl 1), pp. S3-18.
    • Hendrie, H. C. et al. 2001. Incidence of dementia and Alzheimer disease in 2 communities: Yoruba residing in Ibadan, Nigeria, and African Americans residing in Indianapolis, Indiana. Jama 285(6), pp. 739-747.
    • Hill, L. R. et al. 1993. Functional status, education, and the diagnosis of dementia in the Shanghai survey. Neurology 43(1), pp. 138-145.
    • Hiltunen, M. et al. 2001. Genome-wide linkage disequilibrium mapping of late-onset Alzheimer's disease in Finland. Neurology 57(9), pp. 1663-1668.
    • Hirono, N. et al. 1999. Lack of effect of apolipoprotein E E4 allele on neuropsychiatric manifestations in Alzheimer's disease. J Neuropsychiatry Clin Neurosci 11(1), pp. 66-70.
    • Holmans, P. 2003. Nonparametric Linkage. In: Balding, D.J. et al. eds. Handbook o f Statistical Genetics. 2nd Ed. Chichester: Wiley, pp. 919-938.
    • Holmans, P. and Clayton, D. 1995. Efficiency of typing unaffected relatives in an affectedsib-pair linkage study with single-locus and multiple tightly linked markers. Am J Hum Genet 57(5), pp. 1221-1232.
    • Holmes, C. et al. 1999. Validity of current clinical criteria for Alzheimer's disease, vascular dementia and dementia with Lewy bodies. B r J Psychiatry 174, pp. 45-50.
    • Holmes, C. et al. 1996. Apolipoprotein E: non-cognitive symptoms and cognitive decline in late onset Alzheimer's disease. J Neurol Neurosurg Psychiatry 61(6), pp. 580-583.
    • Holmes, C. and Lovestone, S. 2002. The clinical phenotype of familial and sporadic late onset Alzheimer's disease. Int J Geriatr Psychiatry 17(2), pp. 146-149.
    • Holmes, C. et al. 1998b. Apolipoprotein E: depressive illness, depressive symptoms, and Alzheimer's disease. Biol Psychiatry 43(3), pp. 159-164.
    • Holmes, C. et al. 2001. Psychosis and aggression in Alzheimer's disease: the effect of dopamine receptor gene variation. J Neurol Neurosurg Psychiatry 71(6), pp. 777- 779.
    • Hope, T. et al. 1997. Behaviour changes in dementia. 2: Are there behavioural syndromes? In tJ G eriatr Psychiatry 12(11), pp. 1074-1078.
    • Hope, T. et al. 1998. Predictors of institutionalization for people with dementia living at home with a carer. Int J G eriatr Psychiatry 13(10), pp. 682-690.
    • Hughes, C. P. et al. 1982. A new clinical scale for the staging of dementia. B r J Psychiatry 140, pp. 566-572.
    • Humpel, C. and Marksteiner, J. 2005. Cerebrovascular damage as a cause for Alzheimer's disease. Curr Neurovasc Res 2(4), pp. 341-347.
    • Ikeda, M. et al. 2002. Changes in appetite, food preference, and eating habits in frontotemporal dementia and Alzheimer's disease. J Neurol Neurosurg Psychiatry 73(4), pp. 371-376.
    • International Human Genome Sequencing Consortium 2004. Finishing the euchromatic sequence of the human genome. Nature 431(7011), pp. 931-945.
    • Jarvik, G. et al. 1996. Influence of apolipoprotein E genotype on the transmission of Alzheimer disease in a community-based sample. Am J Hum Genet 58(1), pp. 191-200.
    • Jeste, D. V. and Finkel, S. I. 2000. Psychosis of Alzheimer's disease and related dementias. Diagnostic criteria for a distinct syndrome. Am J Geriatr Psychiatry 8(1), pp. 29-34.
    • Jeste, D. V. et al. 1992. Cognitive deficits of patients with Alzheimer's disease with and without delusions. Am J Psychiatry 149(2), pp. 184-189.
    • Jorm, A. F. and Jolley, D. 1998. The incidence of dementia: a meta-analysis. Neurology 51(3), pp. 728-733.
    • Jost, B. C. and Grossberg, G. T. 1995. The natural history of Alzheimer's disease: a brain bank study. J Am G eriatr Soc 43(11), pp. 1248-1255.
    • Kaiser, H. F. 1960. The application of electronic computers to factor analysis. Educational and Psychological M easurem ent 20, pp. 141-151.
    • Kamboh, M. I. 2004. Molecular genetics of late-onset Alzheimer's disease. Ann Hum Genet 68(Pt 4), pp. 381-404.
    • Kanai, M. et al. 1999. Apolipoprotein E4 accelerates dementia and increases cerebrospinal fluid tau levels in Alzheimer's disease. Neurosci Lett 267(1), pp. 65- 68.
    • Kantarci, K. and Jack, C. R., Jr. 2003. Neuroimaging in Alzheimer disease: an evidencebased review. Neuroimaging Clin N Am 13(2), pp. 197-209.
    • Karp, A. et al. 2004. Relation of education and occupation-based socioeconomic status to incident Alzheimer's disease. Am J Epidemiol 159(2), pp. 175-183.
    • Katila, H. et al. 1999. Polymorphisms of the interleukin-1 gene complex in schizophrenia. Mol Psychiatry 4(2), pp. 179-181.
    • Katzman, R. 1993. Education and the prevalence of dementia and Alzheimer's disease. Neurology 43(1), pp. 13-20.
    • Kaufer, D. et al. 1998. Differential neuropsychiatric symptom responses to tacrine in Alzheimer's disease: relationship to dementia severity. J Neuropsychiatry Clin Neurosci 10(1), pp. 55-63.
    • Kawas, C. et al. 2000. Age-specific incidence rates of Alzheimer's disease: the Baltimore Longitudinal Study of Aging. Neurology 54(11), pp. 2072-2077.
    • Kehoe, P. et al. 1999. A full genome scan for late onset Alzheimer's disease. Hum Mol Genet 8(2), pp. 237-245.
    • Kendler, K. S. 1990. Toward a scientific psychiatric nosology. Strengths and limitations. Arch Gen Psychiatry 47(10), pp. 969-973.
    • Kendler, K. S. and Gardner, C. O., Jr. 1998. Twin studies of adult psychiatric and substance dependence disorders: are they biased by differences in the environmental experiences of monozygotic and dizygotic twins in childhood and adolescence? Psychol M ed 28(3), pp. 625-633.
    • Knopman, D. S. et al. 1988. Longitudinal study of death and institutionalization in patients with primary degenerative dementia. J Am Geriatr Soc 36(2), pp. 108-112.
    • Kokmen, E. et al. 1989. Prevalence of medically diagnosed dementia in a defined United States population: Rochester, Minnesota, January 1, 1975. Neurology 39(6), pp. 773-776.
    • Kong, A. et al. 2002. A high-resolution recombination map of the human genome. Nat Genet 31(3), pp. 241-247.
    • Kordower, J. H. et al. 2001. Loss and atrophy of layer II entorhinal cortex neurons in elderly people with mild cognitive impairment. Ann Neurol 49(2), pp. 202-213.
    • Korszun, A. et al. 2004. Familiality of symptom dimensions in depression. Arch Gen Psychiatry 61(5), pp. 468-474.
    • Koss, E. et al. 1996. Clinical and neuropsychological differences between patients with earlier and later onset of Alzheimer's disease: A CERAD analysis, Part XII. Neurology 46(1), pp. 136-141.
    • Krishnan, K. R. et al. 1996. Apolipoprotein E-epsilon 4 frequency in geriatric depression. Biol Psychiatry 40(1), pp. 69-71.
    • Kukull, W. A. et al. 2002. Dementia and Alzheimer disease incidence: a prospective cohort study. Arch Neurol 59(11), pp. 1737-1746.
    • Lam, L. C. et al. 2004. 5-HT2AT102C receptor polymorphism and neuropsychiatric symptoms in Alzheimer's disease. Int J Geriatr Psychiatry 19(6), pp. 523-526.
    • Lambert, D. et al. 2005. Stage 2 of the Wellcome Trust UK-lrish bipolar affective disorder sibling-pair genome screen: evidence for linkage on chromosomes 6q16-q21, 4q12-q21, 9p21, 10p14-p12 and 18q22. Mol Psychiatry 10(9), pp. 831-841.
    • Lambert, J. C. et al. 2002. Contribution of APOE promoter polymorphisms to Alzheimer's disease risk. Neurology 59(1), pp. 59-66.
    • Lambert, J. C. et al. 1998. Pronounced impact of Th1/E47cs mutation compared with -491 AT mutation on neural APOE gene expression and risk of developing Alzheimer's disease. Hum M ol Genet 7(9), pp. 1511-1516.
    • Lanctot, K. L. et al. 2001. Role of serotonin in the behavioral and psychological symptoms of dementia. J Neuropsychiatry Clin Neurosci 13(1), pp. 5-21.
    • Lander, E. and Kruglyak, L. 1995. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet 11(3), pp. 241-247.
    • Lander, E. S. and Schork, N. J. 1994. Genetic dissection of complex traits. Science 265(5181), pp. 2037-2048.
    • Landes, A. M. et al. 2001. Apathy in Alzheimer's disease. J Am Geriatr Soc 49(12), pp. 1700-1707.
    • Lamer, A. J. 2005. "Frontal variant Alzheimer's disease": A reappraisal. Clin Neurol Neurosurg.
    • Larson, E. B. et al. 2004. Survival after initial diagnosis of Alzheimer disease. Ann Intern Med 140(7), pp. 501-509.
    • Launer, L. J. 1992. Overview of incidence studies of dementia conducted in Europe. Neuroepidemiology 11 Suppl 1, pp. 2-13.
    • Launer, L. J. et al. 1999. Rates and risk factors for dementia and Alzheimer's disease: results from EURODEM pooled analyses. EURODEM Incidence Research Group and Work Groups. European Studies of Dementia. Neurology 52(1), pp. 78-84.
    • Lawlor, B. and Bhriain, S. N. 2001. Psychosis and behavioural symptoms of dementia: defining the role of neuroleptic interventions. Int J Geriatr Psychiatry 16 Suppl 1, pp. S2-6.
    • Lawlor, B. A. et al. 1994. Clinical symptoms associated with age at onset in Alzheimer's disease. Am J Psychiatry 151(11), pp. 1646-1649.
    • Leboyer, M. et al. 1998. Psychiatric genetics: search for phenotypes. Trends Neurosci 21(3), pp. 102-105.
    • Leckman, J. F. et al. 1984. Subtypes of depression. Family study perspective. Arch Gen Psychiatry 41(9), pp. 833-838.
    • Lee, J. H. et al. 2004. Fine mapping of 10q and 18q for familial Alzheimer's disease in Caribbean Hispanics. M ol Psychiatry 9(11), pp. 1042-1051.
    • Lee, P. N. 1994. Smoking and Alzheimer's disease: a review of the epidemiological evidence. Neuroepidem iology 13(4), pp. 131-144.
    • Lehtovirta, M. et al. 1996a. Clinical and neuropsychological characteristics in familial and sporadic Alzheimer's disease: relation to apolipoprotein E polymorphism. Neurology 46(2), pp. 413-419.
    • Lehtovirta, M. et al. 1996b. SPECT and MRI analysis in Alzheimer's disease: relation to apolipoprotein E epsilon 4 allele. J Neurol Neurosurg Psychiatry 60(6), pp. 644- 649.
    • Lendon, C. L. et al. 1997. Exploring the etiology of Alzheimer disease using molecular genetics. Jama 277(10), pp. 825-831.
    • Letenneur, L. et al. 1994a. Incidence of dementia and Alzheimer's disease in elderly community residents of south-western France. Int J Epidemiol 23(6), pp. 1256- 1261.
    • Letenneur, L. et al. 1994b. Tobacco consumption and cognitive impairment in elderly people. A population-based study. Ann Epidemiol 4(6), pp. 449-454.
    • Levinson, D. F. et al. 2000. Multicenter linkage study of schizophrenia candidate regions on chromosomes 5q, 6q, 10p, and 13q: schizophrenia linkage collaborative group III. Am J Hum Genet 67(3), pp. 652-663.
    • Levy, M. L. et al. 1996a. Longitudinal assessment of symptoms of depression, agitation, and psychosis in 181 patients with Alzheimer's disease. Am J Psychiatry 153(11), pp. 1438-1443.
    • Levy, M. L. et al. 1999. Apolipoprotein E genotype and noncognitive symptoms in Alzheimer's disease. Biol Psychiatry 45(4), pp. 422-425.
    • Levy, M. L. et al. 1996b. Alzheimer disease and frontotemporal dementias. Behavioral distinctions. Arch Neurol 53(7), pp. 687-690.
    • Levy-Lahad, E. et al. 1995a. Apolipoprotein E genotypes and age of onset in early-onset familial Alzheimer's disease. Ann Neurol 38(4), pp. 678-680.
    • Levy-Lahad, E. et al. 1995b. Candidate gene for the chromosome 1 familial Alzheimer's disease locus. Science 269(5226), pp. 973-977.
    • Li, Y. J. et al. 2002. Age at onset in two common neurodegenerative diseases is genetically controlled. Am J Hum Genet 70(4), pp. 985-993.
    • Lineweaver, T. T. et al. 2005. Differential effects of Alzheimer's disease and Huntington's disease on the performance of mental rotation. J Int Neuropsychol Soc 11(1), pp. 30-39.
    • Lippa, C. F. 1999. Familial Alzheimer's disease: genetic influences on the disease process (Review). Int J M ol M ed 4(5), pp. 529-536.
    • Liu, L. et al. 1996. Allelic association but only weak evidence for linkage to the apolipoprotein E locus in late-onset Swedish Alzheimer families. Am J Med Genet 67(3), pp. 306-311.
    • Lopez, O. L. et al. 1991. Alzheimer's disease with delusions and hallucinations: neuropsychological and electroencephalographic correlates. Neurology 41(6), pp. 906-912.
    • Lopez, O. L. et al. 2003. Psychiatric symptoms vary with the severity of dementia in probable Alzheimer's disease. J Neuropsychiatry Clin Neurosci 15(3), pp. 346-353.
    • Lopez, O. L. et al. 1997. The apolipoprotein E epsilon 4 allele is not associated with psychiatric symptoms or extrapyramidal signs in probable Alzheimer's disease. Neurology 49(3), pp. 794-797.
    • Lopez, O. L. et al. 1999. Psychiatric medication and abnormal behavior as predictors of progression in probable Alzheimer disease. Arch Neurol 56(10), pp. 1266-1272.
    • Lovestone, S. and Hardy, J. 2002. Psychotic genes or forgetful ones? Neurology 59(1), pp. 11-12.
    • Luchsinger, J. A. and Mayeux, R. 2004. Cardiovascular risk factors and Alzheimer's disease. Curr Atheroscler Rep 6(4), pp. 261-266.
    • Lucotte, G. et al. 1994. Apolipoprotein E-epsilon 4 allele doses in late-onset Alzheimer's disease. Ann Neurol 36(4), pp. 681-682.
    • Lyketsos, C. G. et al. 1997. Depression, delusions, and hallucinations in Alzheimer's disease: no relationship to apolipoprotein E genotype. J Neuropsychiatry Clin Neurosci 9(1), pp. 64-67.
    • Lyketsos, C. G. et al. 1999. Physical aggression in dementia patients and its relationship to depression. Am J Psychiatry 156(1), pp. 66-71.
    • Lyketsos, C. G. et al. 2000. Mental and behavioral disturbances in dementia: findings from the Cache County Study on Memory in Aging. Am J Psychiatry 157(5), pp. 708- 714.
    • Lyketsos, C. G. et al. 1996. Major depression in Alzheimer's disease. An interaction between gender and family history. Psychosomatics 37(4), pp. 380-384.
    • Mack, J. L. et al. 1999. Behavior Rating Scale for Dementia: development of test scales and presentation of data for 555 individuals with Alzheimer's disease. J Geriatr Psychiatry Neurol 12(4), pp. 211-223.
    • Magni, E. et al. 1996. Risk of mortality and institutionalization in demented patients with delusions. J G eriatr Psychiatry Neurol 9(3), pp. 123-126.
    • Manuck, S. B. et al. 1999. Aggression and anger-related traits associated with a polymorphism of the tryptophan hydroxylase gene. Biol Psychiatry 45(5), pp. 603- 614.
    • Marin, D. B. et al. 1997. Noncognitive disturbances in Alzheimer's disease: frequency, longitudinal course, and relationship to cognitive symptoms. J Am Geriatr Soc 45(11), pp. 1331-1338.
    • Marin, R. S. et al. 1994. Group differences in the relationship between apathy and depression. J Nerv M e n tD is 182(4), pp. 235-239.
    • Martinez, M. et al. 1998. Apolipoprotein E epsilon4 allele and familial aggregation of Alzheimer disease. Arch Neurol 55(6), pp. 810-816.
    • Martinez, M. et al. 1999. Follow-up study on a susceptibility locus for schizophrenia on chromosome 6q. Am J M ed Genet 88(4), pp. 337-343.
    • Matsuda, O. and Saito, M. 2005. Functional competency and cognitive ability in mild Alzheimer's disease: relationship between ADL assessed by a relative/ carer-rated scale and neuropsychological performance. Int Psychogeriatr 17(2), pp. 275-288.
    • Matsuoka, K. et al. 2003. Relationship between behavioral disturbances and characteristics of patients in special units for dementia. Psychiatry Clin Neurosci 57(6), pp. 569-574.
    • McCurry, S. M. et al. 2004. Anxiety and nighttime behavioral disturbances. Awakenings in patients with Alzheimer's disease. J Gerontol Nurs 30(1), pp. 12-20.
    • Mcllroy, S. and Craig, D. 2004. Neurobiology and genetics of behavioural syndromes of Alzheimer's disease. Curr Alzheimer Res 1(2), pp. 135-142.
    • McKhann, G. et al. 1984. Clinical diagnosis of Alzheimer's disease: report of the NINCDSADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 34(7), pp. 939-944.
    • McQueen, M. B. et al. 2005. Combined analysis from eleven linkage studies of bipolar disorder provides strong evidence of susceptibility loci on chromosomes 6q and 8q. Am J Hum Genet 77(4), pp. 582-595.
    • McShane, R. 2000. What are the behavioral and psychological symptoms in dementia? Int Psychogeriatr 12(Suppl 1), pp. 147-153.
    • McShane, R. et al. 1997. Do neuroleptic drugs hasten cognitive decline in dementia? Prospective study with necropsy follow up. Bmj 314(7076), pp. 266-270.
    • Mega, M. S. et al. 1996. The spectrum of behavioral changes in Alzheimer's disease. Neurology 46(1), pp. 130-135.
    • Merikangas, K. R. et al. 1989. Linkage studies of bipolar disorder: methodologic and analytic issues. Report of MacArthur Foundation Workshop on Linkage and Clinical Features in Affective Disorders. Arch Gen Psychiatry 46(12), pp. 1137- 1141.
    • Meyer, M. R. et al. 1998. APOE genotype predicts when--not whether--one is predisposed to develop Alzheimer disease. Nat Genet 19(4), pp. 321-322.
    • Middeldorp, C. M. et al. 2005. The co-morbidity of anxiety and depression in the perspective of genetic epidemiology. A review of twin and family studies. Psychol Med 35(5), pp. 611-624.
    • Miech, R. A. et al. 2002. Incidence of AD may decline in the early 90s for men, later for women: The Cache County study. Neurology 58(2), pp. 209-218.
    • Migliorelli, R. et al. 1995a. Neuropsychiatric and neuropsychological correlates of delusions in Alzheimer's disease. Psychol Med 25(3), pp. 505-513.
    • Migliorelli, R. et al. 1995b. Prevalence and correlates of dysthymia and major depression among patients with Alzheimer's disease. Am J Psychiatry 152(1), pp. 37-44.
    • Mintzer, J. et al. 2001. Olanzapine in the treatment of anxiety symptoms due to Alzheimer's disease: a post hoc analysis. Int J Geriatr Psychiatry 16 Suppl 1, pp. S71-77.
    • Mirakhur, A. et al. 2004. Behavioural and psychological syndromes in Alzheimer's disease. Int J G eriatr Psychiatry 19(11), pp. 1035-1039.
    • Moran, M. et al. 2004. Syndromes of behavioural and psychological symptoms in mild Alzheimer's disease. In tJ Geriatr Psychiatry 19(4), pp. 359-364.
    • Mori, E. et al. 2002. Accelerated hippocampal atrophy in Alzheimer's disease with apolipoprotein E epsilon4 allele. Ann Neurol 51(2), pp. 209-214.
    • Morris, J. C. et al. 1989. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer's disease. Neurology 39(9), pp. 1159-1165.
    • Mortel, K. F. et al. 1995. Education and occupation as risk factors for dementias of the Alzheimer and ischemic vascular types. Dementia 6(1), pp. 55-62.
    • Mortimer, J. A. et al. 2003. Head circumference, education and risk of dementia: findings from the Nun Study. J Clin Exp Neuropsychol 25(5), pp. 671-679.
    • Mourik, J. C. et al. 2004. Frontotemporal dementia: behavioral symptoms and caregiver distress. Dement Geriatr Cogn Disord 18(3-4), pp. 299-306.
    • Mullan, M. et al. 1993. Age of onset in familial early onset Alzheimer's disease correlates with genetic aetiology. Am J M ed Genet 48(3), pp. 129-130.
    • Muller-Thomsen, T. et al. 2002. Depression in Alzheimer's disease might be associated with apolipoprotein E epsilon 4 allele frequency in women but not in men. Dement Geriatr Cogn Disord 14(2), pp. 59-63.
    • Myers, A. et al. 2000. Susceptibility locus for Alzheimer's disease on chromosome 10. Science 290(5500), pp. 2304-2305.
    • Myers, A. et al. 2002. Full genome screen for Alzheimer disease: stage II analysis. Am J Med Genet 114(2), pp. 235-244.
    • Myers, R. H. et al. 1996. Apolipoprotein E epsilon4 association with dementia in a population-based study: The Framingham study. Neurology 46(3), pp. 673-677.
    • Nacmias, B. et al. 1999. 5-HT2A receptor gene polymorphisms in anorexia nervosa and bulimia nervosa. Neurosci Lett 277(2), pp. 134-136.
    • Nacmias, B. et al. 2001. Association between 5-HT(2A) receptor polymorphism and psychotic symptoms in Alzheimer's disease. Biol Psychiatry 50(6), pp. 472-475.
    • Nalbantoglu, J. et al. 1994. Predictive value of apolipoprotein E genotyping in Alzheimer's disease: results of an autopsy series and an analysis of several combined studies. Ann Neurol 36(6), pp. 889-895.
    • Neary, D. et al. 2005. Frontotemporal dementia. Lancet Neurol 4(11), pp. 771-780.
    • Nee, L. E. et al. 1987. Dementia of the Alzheimer type: clinical and family study of 22 twin pairs. Neurology 37(3), pp. 359-363.
    • Nussbaum, R. L. and Ellis, C. E. 2003. Alzheimer's disease and Parkinson's disease. N Engl J M ed 348(14), pp. 1356-1364.
    • O'Connell, J. R. and Weeks, D. E. 1998. PedCheck: a program for identification of genotype incompatibilities in linkage analysis. Am J Hum Genet 63(1), pp. 259- 266.
    • Pauls, D. L. et al. 1995. A family study of obsessive-compulsive disorder. Am J Psychiatry 152(1), pp. 76-84.
    • Paulsen, J. S. et al. 2000. Incidence of and risk factors for hallucinations and delusions in patients with probable AD. Neurology 54(10), pp. 1965-1971.
    • Payami, H. et al. 1997. A prospective study of cognitive health in the elderly (Oregon Brain Aging Study): effects of family history and apolipoprotein E genotype. Am J Hum Genet 60(4), pp. 948-956.
    • Paykel, E. S. et al. 1994. Incidence of dementia in a population older than 75 years in the United Kingdom. Arch Gen Psychiatry 51(4), pp. 325-332.
    • Paykel, E. S. et al. 1998. Incidence of dementia and cognitive decline in over-75s in Cambridge: overview of cohort study. Soc Psychiatry Psychiatr Epidemiol 33(8), pp. 387-392.
    • Potash, J. B. et al. 2001. The familial aggregation of psychotic symptoms in bipolar disorder pedigrees. Am J Psychiatry 158(8), pp. 1258-1264.
    • Pritchard, J. K. 2001. Are rare variants responsible for susceptibility to complex diseases? Am J Hum Genet 69(1), pp. 124-137.
    • Procter, A. W. et al. 1992. Serotonergic pathology is not widespread in Alzheimer patients without prominent aggressive symptoms. Neurochem Res 17(9), pp. 917-922.
    • Purandare, N. et al. 2001. Depressive symptoms in patients with Alzheimer's disease. Int J Geriatr Psychiatry 16(10), pp. 960-964.
    • Wu, W S et al 1998a Genetic studies on chromosome 12 in late-onset Alzheimer disease Jama 280(7), pp 619-622
  • No related research data.
  • No similar publications.

Share - Bookmark

Funded by projects

  • WT

Cite this article

Cookies make it easier for us to provide you with our services. With the usage of our services you permit us to use cookies.
More information Ok