Midlife Metabolic Profile and the Risk of Late-Life Cognitive Decline

Article type: Research Article

Authors: Tortelli, Rosanna^a | Lozupone, Madia^b | Guerra, Vito^c | Barulli, Maria Rosaria^a | Imbimbo, Bruno P.^d | Capozzo, Rosa^a | Grasso, Alessandra^b | Tursi, Marianna^b | Di Dio, Cristina^a | Sardone, Rodolfo^c | Giannelli, Gianluigi^c | Seripa, Davide^e | Misciagna, Giovanni^c | Panza, Francesco^{a; b; e; *} | Logroscino, Giancarlo^{a; b; *}

Affiliations: [a] Department of Clinical Research in Neurology, Unit of Neurodegenerative Disease, University of Bari “Aldo Moro” at “Pia Fondazione Card. G. Panico”, Tricase, Lecce, Italy | [b] Department of Basic Medicine, Neurodegenerative Disease Unit, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy | [c] National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, Castellana Grotte Bari, Italy | [d] Department of Research & Development, Chiesi Farmaceutici, Parma, Italy | [e] Department of Medical Sciences, Geriatric Unit and Gerontology-Geriatrics Research Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy

Correspondence: [*] Correspondence to: Francesco Panza, MD, PhD and Giancarlo Logroscino, MD, PhD, Department of Basic Medicine, Neurodegenerative Disease Unit, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy and Department of Clinical Research in Neurology, University of Bari Aldo Moro, “Pia Fondazione Cardinale G. Panico”, Tricase, Lecce, Italy. Tel.: +39 0883 773904; Fax: +39 0883 773909; E-mails: geriat.dot@uniba.it (Francesco Panza) and giancarlo.logroscino@uniba.it (Giancarlo Logroscino).

Abstract: Among metabolic syndrome components, the effects of higher plasma glucose levels on cognitive decline (CD) have been considered in few studies. We evaluated the associations among midlife glycemia, total cholesterol, high-density lipoprotein cholesterol, triglycerides, midlife insulin resistance [homeostasis model assessment for insulin resistance (HOMA-index)], and CD in the older subjects of the population-based MICOL Study (Castellana Grotte, Italy) at baseline (M1) and at follow-ups seven (M2) and twenty years later (M3). At M1, a dementia risk score and a composite cardiovascular risk score for dementia were calculated. For 797 subjects out of 833, we obtained a Mini-Mental State Examination (MMSE) score at M3, subdividing these subjects in three cognitive functioning subgroups: normal cognition, mild CD, and moderate-severe CD. Mean fasting glycemia at baseline was significantly higher in moderate-severe CD subgroup (114.6±71.4 mg/dl) than in the normal cognition subgroup (101.2±20.6). Adjusting for gender, age, and other metabolic components, higher fasting glycemia values both at M1 [odds ratio (OR) = 1.31; 95% confidence interval (CI): 1.08–1.59] and M2 (OR = 1.26; 95% CI: 1.01–1.57) were associated with an increased risk of moderate-severe CD. Mean HOMA index value was significantly higher in the moderate-severe CD subgroup (5.7±9.4) compared to the normal cognition subgroup (2.9±1.4) at M1. The dementia risk probability (MMSE < 24) increased moving through higher categories of the dementia risk score and decreased as long as the cardiovascular score increased. The present findings highlighted the indication to control blood glucose levels, regardless of a diagnosis of diabetes mellitus, as early as midlife for prevention of late-life dementia.

Keywords: Alzheimer’s disease, cognitive decline, dementia risk scores, diabetes mellitus, fasting glycemia, GreatAGE Study, insulin resistance, metabolic syndrome, nutrition

DOI: 10.3233/JAD-170153

Journal: Journal of Alzheimer's Disease, vol. 59, no. 1, pp. 121-130, 2017