The proposed research aims to clarify the relationship between the major histo-compatibility gene complex, HLA, and Dementia of the Alzheimer Type (DAT). Previous research has indicated that genetic and immunological factors are involved in DAT and that the HLA gene complex is related to immunological mechanisms and various neurological diseases of unknown origin. These studies led to preliminary research on the association between HLA typing and DAT. Although together the studies of DAT/HLA associations suggest a relationship between specific HLA antigens and DAT, some of the results are conflicting. Methodological difficulties may explain the discrepancies; for example patients with both dementia and depression (another psychiatric illness related to the HLA gene complex) are generally not segregated out or even identified. The proposed research will, therefore, investigate HLA typing in four groups of subjects as carefully defined as the state of the art permits: (1) patients with DAT; (2) patients with DAT and concurrent symptoms compatible with Major Depressive Disorder; (3) patients with Major Depressive Disorder alone; and (4) matched controls. In addition, first-degree relatives, when available, will be studied. A substantial number of subjects (group 2) will show features of both cognitive deficit and depression. Because no large-scale longitudinal studies have yet clarified these kinds of patients with overlapping symptoms, neuropsychological and psychosocial profiles will be collected to improve our understanding and clinical descriptions of such patients. The cause or causes of DAT remain(s) unknown; most likely they are multiple. The presence of HLA/DAT associations may be useful in distinguishing homogeneous subgroups among patients with DAT, homogeneity which could be of inestimable value with respect to treatment, outcome, and prediction of risk in as yet unaffected individuals. HLA associations with particular subgroups of patients with DAT offers, therefore, the possibility of refining our definition of a relatively global and heterogeneous syndrome into more specific disease entities.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AG000200-04
Application #
3078429
Study Section
Aging Review Committee (AGE)
Project Start
1983-03-01
Project End
1988-02-29
Budget Start
1986-03-01
Budget End
1987-02-28
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Small, G W; Kuhl, D E; Riege, W H et al. (1989) Cerebral glucose metabolic patterns in Alzheimer's disease. Effect of gender and age at dementia onset. Arch Gen Psychiatry 46:527-32
Small, G W (1988) Psychopharmacological treatment of elderly demented patients. J Clin Psychiatry 49 Suppl:8-13
Small, G W; Fong, K; Beck, J C (1988) Training in geriatric psychiatry: will the supply meet the demand? Am J Psychiatry 145:476-8
Small, G W; Kuhl, D E; Fujikawa, D G et al. (1988) Clinical characterization of Alzheimer's disease: reliability of 'age at onset' and a new descriptor, 'age at shift'. J Geriatr Psychiatry Neurol 1:207-11
Small, G W; Greenberg, D A (1988) Biologic markers, genetics, and Alzheimer's disease. Arch Gen Psychiatry 45:945-7
Small, G W; Matsuyama, S S (1986) HLA-A2 as a possible marker for early-onset Alzheimer disease in men. Neurobiol Aging 7:211-4
Small, G W; Komanduri, R (1986) Physical symptoms in patients with primary degenerative dementia. Compr Psychiatry 27:540-4
Small, G W; Matsuyama, S S; Komanduri, R et al. (1985) Thyroid disease in patients with dementia of the Alzheimer type. J Am Geriatr Soc 33:538-9
Small, G W (1985) Revised Ischemic Score for diagnosing multi-infarct dementia. J Clin Psychiatry 46:514-7