Gender-related effect of clinical and genetic variables on the cognitive impairment in multiple sclerosis.
BACKGROUND
Cognitive impairment may occur at any time during the course of multiple sclerosis (MS), and it is often a major cause of disability in patients with the disease. The APOE-epsilon4 allele is the major known genetic risk factor for late onset familial and sporadic Alzheimer's Disease (AD), and it seems to be implicated in cognitive decline in normal elderly persons.


OBJECTIVE
To investigate the clinical and genetic variables that can be associated with the cognitive decline in patients with MS.


METHODS
Five-hundred and three patients with clinically definite MS underwent a battery of neuropsychological tests and, according to the number of failed tests, were divided into cognitively normal and impaired. All patients were genotyped for APOE gene polymorphisms.


RESULTS
Fifty-six percent of MS patients showed, to different extents, cognitive impairment. Cognitive decline was predominant in men and was associated with disease duration, Kurtzke Expanded Disability Status Scale (EDSS) score, a low level of education, and, interestingly, the epsilon4 allele of the APOE gene. By contrast, cognitive impairment in women was independent of any investigated variable.


CONCLUSIONS
The findings demonstrate that clinical and genetic factors play a role in men affected by MS developing cognitive impairment.
Savettieri
Giovanni
G
Institute of Neuropsychiatry, University of Palermo, Palermo, Italy.
Messina
Demetrio
D
Andreoli
Virginia
V
Bonavita
Simona
S
Caltagirone
Carlo
C
Cittadella
Rita
R
Farina
Deborah
D
Fazio
Maria Carolina
MC
Girlanda
Paolo
P
Le Pira
Francesco
F
Liguori
Maria
M
Lugaresi
Alessandra
A
Nocentini
Ugo
U
Reggio
Arturo
A
Salemi
Giuseppe
G
Tedeschi
Gioacchino
G
Trojano
Maria
M
Valentino
Paola
P
Quattrone
Aldo
A
D000328:Adult; D000704:Analysis of Variance; D001057:Apolipoproteins E / Q000235:genetics; D016009:Chi-Square Distribution; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000235:genetics*; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D016017:Odds Ratio; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012727:Sex Characteristics
D001057:Apolipoproteins E; D012333:RNA, Messenger