Apolipoprotein E Genotype and Cerebrovascular Alterations Can Influence Conversion to Dementia in Patients with Mild Cognitive Impairment

Article type: Research Article

Authors: Viticchi, Giovanna^a | Falsetti, Lorenzo^b | Vernieri, Fabrizio^c | Altamura, Claudia^c | Altavilla, Riccardo^c | Luzzi, Simona^a | Bartolini, Marco^a | Provinciali, Leandro^a | Silvestrini, Mauro^{a; *}

Affiliations: [a] Neurological Clinic, Marche Polytechnic University, Ancona, Italy | [b] Internal and Subintensive Medicine, Ospedali Riuniti Ancona, Italy | [c] Neurology Unit, Campus Bio-Medico University, Rome, Italy

Correspondence: [*] Correspondence to: Mauro Silvestrini, Neurological Clinic, Marche Polytechnic University, Via Conca 1, 60020 Ancona, Italy. Tel.: +39 071 596 5668; Fax: +39 071 887262; E-mail: [email protected].

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.

Keywords: Alzheimer's disease, apolipoproteins E, cerebrovascular diseases, cognition, ultrasonography

DOI: 10.3233/JAD-132480

Journal: Journal of Alzheimer's Disease, vol. 41, no. 2, pp. 401-410, 2014