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Authors: Cocks, Graham | Wilde, Jonathan I. | Graham, Simon J | Bousgouni, Vicky | Virley, David | Lovestone, Simon | Richardson, Jill

Article Type: Research Article

Abstract: In a recent clinical study, the thiazolidinedione (TZD) pioglitazone (Actos™ was reported to preserve cognitive function in patients with mild to moderate Alzheimer's disease and type II diabetes mellitus. TZDs are agonists of the nuclear hormone receptor peroxisome proliferator-activated receptor-γ (PPARγ), are peripheral insulin sensitizers, and have recently been reported to increase mitochondrial biogenesis in the central nervous system and dendritic spine density. We report a transcriptional profile of the TZD pioglitazone and the non-TZD PPARγ agonist GW347845 in primary cortical culture. We observed that pioglitazone, but not GW347845, increased cholesterol biosynthetic and lipogenic gene expression after 6 h, and …the expression of the cholesterol efflux transporters Abca1 and Abcg1 after 24 h. Co-treatment of pioglitazone with the PPARγ antagonist GW9662 did not significantly reduce these effects, suggesting a PPARγ-independent mechanism. These findings suggest a novel effect of TZDs in neurons that may be of relevance as a novel approach against Alzheimer's disease. Show more

Keywords: ABCA1, Alzheimer's disease, cholesterol biosynthesis, thiazolidinediones

DOI: 10.3233/JAD-2010-1266

Citation: Journal of Alzheimer's Disease, vol. 19, no. 2, pp. 631-646, 2010

Authors: Hird, Megan A. | Vesely, Kristin A. | Fischer, Corinne E. | Graham, Simon J. | Naglie, Gary | Schweizer, Tom A.

Article Type: Short Communication

Abstract: The areas of driving impairment characteristic of mild cognitive impairment (MCI) remain unclear. This study compared the simulated driving performance of 24 individuals with MCI, including amnestic single-domain (sd-MCI, n  = 11) and amnestic multiple-domain MCI (md-MCI, n  = 13), and 20 age-matched controls. Individuals with MCI committed over twice as many driving errors (20.0 versus 9.9), demonstrated difficulty with lane maintenance, and committed more errors during left turns with traffic compared to healthy controls. Specifically, individuals with md-MCI demonstrated greater driving difficulty compared to healthy controls, relative to those with sd-MCI. Differentiating between different subtypes of MCI may be important when …evaluating driving safety. Show more

Keywords: Automobile driving, cognition, computer simulation patient outcome assessment, mild cognitive impairment

DOI: 10.3233/JAD-160995

Citation: Journal of Alzheimer's Disease, vol. 56, no. 2, pp. 447-452, 2017