title: Apolipoprotein E genotype and cerebrovascular alterations can influence conversion to dementia in patients with mild cognitive impairment.
abstract: The presence of apolipoprotein E (APOE) ε4 allele is the only recognized genetic risk factor for the sporadic form of Alzheimer's disease. The aim of this study was to investigate the relationship between APOE genotype and the functional and anatomic status of cerebral vessels in patients with mild cognitive impairment (MCI). Moreover, we explored whether the possible correlation between APOE genotype and cerebrovascular parameters influences the risk of conversion from MCI to dementia. 75 MCI patients underwent a complete neuropsychological battery at baseline and after 24 months to evaluate the possible conversion to dementia. Ultrasound assessment of neck and intracranial vessels was performed to assess common carotid artery intima-media thickness (IMT), plaque index, and cerebrovascular reactivity (breath-holding index, BHI). APOE genotype was determined to classify patients as carriers (APOE ε4+) and non-carriers (APOE ε4-). Pathologic values of BHI and IMT were significantly more common in ε4 carriers than in non-carriers [OR 6.603 (95% CI: 1.678-25.997), p < 0.05 and OR 5.195 (95% CI 1.319-20.464), p < 0.05; logistic regression adjusted model]. The risk of conversion to dementia was significantly higher in APOE ε4+ patients than in APOE ε4- ones (OR: 6.818; 95% CI:1.894-24.545, p = 0.003). A path-analysis model showed that APOE genotype influences the progression to dementia directly and indirectly by increasing the risk of pathologic values of IMT or BHI. Our data, besides confirming an increased susceptibility of MCI patients with APOE ε4 to develop dementia, show an association between functional and anatomic impairment of the cerebral vessels and APOE ε4+ genotype.
authors.affiliation: Neurological Clinic, Marche Polytechnic University, Ancona, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Viticchi
authors.affiliation: Internal and Subintensive Medicine, Ospedali Riuniti Ancona, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Falsetti
authors.affiliation: Neurology Unit, Campus Bio-Medico University, Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Vernieri
authors.affiliation: Neurology Unit, Campus Bio-Medico University, Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Altamura
authors.affiliation: Neurology Unit, Campus Bio-Medico University, Rome, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Altavilla
authors.affiliation: Neurological Clinic, Marche Polytechnic University, Ancona, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Luzzi
authors.affiliation: Neurological Clinic, Marche Polytechnic University, Ancona, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Bartolini
authors.affiliation: Neurological Clinic, Marche Polytechnic University, Ancona, Italy.
authors.forename: Leandro
authors.initials: L
authors.lastname: Provinciali
authors.affiliation: Neurological Clinic, Marche Polytechnic University, Ancona, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Silvestrini
mesh_terms: D000368:Aged; D053327:Apolipoprotein E4 / Q000235:genetics*; D001921:Brain / Q000098:blood supply* / Q000503:physiopathology; D062485:Breath Holding; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000503:physiopathology; D003704:Dementia / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000503:physiopathology; D018450:Disease Progression; D004453:Echoencephalography; D005260:Female; D005500:Follow-Up Studies; D006579:Heterozygote; D006801:Humans; D008297:Male; D009333:Neck / Q000098:blood supply / Q000000981:diagnostic imaging; D009483:Neuropsychological Tests; D009929:Organ Size; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging
chemical_list: D053327:Apolipoprotein E4
keywords: Alzheimer's disease; apolipoproteins E; cerebrovascular diseases; cognition; ultrasonography