الفهرس 
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Abstract
Alzheimer’s disease is the most common form of dementia, characterized by slow, progressive memory loss. As the disease progress other symptoms such
as visuospatial disorientation, language impairment, executive dysfunction or
frontal lobe signs develop. Also, there is significant impairment of ADL and
IADL of these patients.
Approximately 5% of people 65 years or older are at risk for developing
Alzheimer’s dementia. The number of Americans with Alzheimer’s disease is
expected to increase to 14 million by 2050, unless a cure or preventive
measures can be found.
This thesis aimed to study the role of TNF α 308 G/A polymorphism in the
development of late onset Alzheimer’s disease (LOAD) in Egyptians.
Our hypothesis was that, the presence of TNF α 308 A allele itself does not
necessarily lead to development of AD, however; it leads to increased
susceptibility to develop Alzheimer’s disease as it is associated with increased
transcriptional activity & elevated levels of TNF.
Sixty two elderly subjects aged ≥65 years participated in this study. The
subjects were divided in two groups matched for age and gender.
(A) Patients group:
31 elderly patients (mean age was about 75 years) diagnosed as probable
Alzheimer’s disease according to The DSM-IV-TR and the NINCDS-ADRDA.
The severity of dementia was staged according to Clinical Dementia Rating
scale (CDRS), Activities of Daily Living (ADL) & Instrumental Activities of
Daily Living (IADL).
(B) Control group:
31 cognitively normal elderly subjects (mean age was about 74 years) with
no evidence of any neurological or psychiatric diseases, or any medical illness
that could affect cognition.
After taking consent, and doing complete medical & neurological
examination, neuropsychological assessment using Mini Mental State
Examination (MMSE), Clock Drawing Test (CDT), Clinical Dementia Rating
Scale (CDRS), Activities of Daily Living (ADL) & Instrumental Activities of
Daily living (IADL) was done for all subjects.
Both cases & control groups had underwent assays for detecting TNF α 308
G/A genotyping by PCR – RFLP method.
The current study revealed that TNF 308 ”A” allele was associated with
increased susceptibility of developing , early age of onset and more severe form
of LOAD in Egyptians as we found that:-
1- The ”A” allele was significantly more prevalent in patients than controls &
the ”G” allele was significantly more prevalent in controls than patients (p <
0.001).
2- The ”A” allele was significantly associated with younger age of onset of AD than the ”G” allele (p < 0.001).
3- The ”A” allele was significantly associated with longer illness duration of
AD than the ”G” allele (p < 0.001).
4- The ”A” allele was significantly associated with higher CDRS score than the
”G” allele denoting more severe form of AD (p < 0.001).
5- The ”A” allele was significantly associated with lower IADL score than the
”G” allele meaning that the ”A” allele is significantly associated with more
functional deterioration among patients denoting more severe form of AD (p 0.001)