title: Longitudinal lipid profile variations and clinical change in Alzheimer's disease dementia.
abstract: Hypercholesterolemia and statin use have been unevenly associated with clinical change in Alzheimer's disease dementia. In this longitudinal study, 192 consecutive outpatients with late-onset Alzheimer's disease dementia were stratified according to APOE haplotypes, and followed for one year to investigate associations of lipid profile variations and lipophilic statin therapy with changes in cognition, caregiver burden, basic and instrumental functionality. Overall, 102 patients (53.1%) carried APOE4+ haplotypes and 90 (46.9%) carried APOE4- haplotypes; 189 patients (98.4%) used either a cholinesterase inhibitor, or Memantine, or both; 144 patients had dyslipidemias and 143 of them received statin therapy. Total cholesterol, LDL-cholesterol, Mini-Mental State Examination scores, and functional independence scores were significantly lower at the end of the follow-up, while Clinical Dementia Rating sum-of-boxes scores were higher. Exclusively for APOE4- carriers, rising LDL-cholesterol levels were associated with a trend toward improvements in the Index of Independence in Activities of Daily Living (β=0.010; ρ=0.16), whereas rising HDL-cholesterol levels were associated with lowered scores (β=-0.051; ρ=0.04). Lipophilic statin therapy had non-significant protective effects over Clinical Dementia Rating sum-of-boxes score variations only for APOE4- carriers. APOE4- haplotypes might enhance lipid availability to protect neuronal membranes, thus overcoming their supposed dysfunction in cholesterol metabolism, while APOE4+ carriers have inefficient neural repair mechanisms. In conclusion, APOE haplotypes seem to influence the protective effects of lipid profile variations for patients with Alzheimer's disease dementia, but current evidence is insufficient to propose lipid-lowering drugs as specific anti-dementia therapy.
authors.affiliation: Department of Neurology and Neurosurgery, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil. Electronic address: fabricioferreiradeoliveira@hotmail.com.
authors.forename: Fabricio Ferreira
authors.initials: FF
authors.lastname: de Oliveira
authors.affiliation: Department of Morphology and Genetics, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil. Electronic address: eschen@unifesp.br.
authors.forename: Elizabeth Suchi
authors.initials: ES
authors.lastname: Chen
authors.affiliation: Department of Morphology and Genetics, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil. Electronic address: macsmith@unifesp.br.
authors.forename: Marilia Cardoso
authors.initials: MC
authors.lastname: Smith
authors.affiliation: Department of Neurology and Neurosurgery, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil. Electronic address: bertolucci.paulo@unifesp.br.
authors.forename: Paulo Henrique Ferreira
authors.initials: PHF
authors.lastname: Bertolucci
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects; D008137:Longitudinal Studies; D008297:Male; D008559:Memantine / Q000494:pharmacology
chemical_list: D053327:Apolipoprotein E4; D002800:Cholinesterase Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008559:Memantine
keywords: Alzheimer Disease; Cholesterol; Dementia; Drug therapy; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Neuropsychiatry