A prospective analysis of elevated fasting glucose levels and cognitive function in older people: results from PROSPER and the Rotterdam Study.
OBJECTIVE
To investigate the relationship between fasting glucose levels, insulin resistance, and cognitive impairment in old age. Diabetes is associated with cognitive impairment in older people. However, the link between elevated fasting glucose levels and insulin resistance in nondiabetic individuals, and the risk of cognitive impairment is unclear.


METHODS
We analyzed data from, in total, 8,447 participants in two independent prospective studies: the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), 5,019 participants, aged 69-84 years, and the Rotterdam Study, 3,428 participants, aged 61-97 years. Fasting glucose levels were assessed at baseline in both studies; fasting insulin levels were assessed in the Rotterdam Study only. Cognitive function was assessed in both studies at baseline and during follow-up.


RESULTS
Subjects with diabetes had impaired cognitive function at baseline. In contrast, in people without a history of diabetes, there was no clear association between baseline fasting glucose levels and executive function and memory, nor was there a consistent relationship between elevated baseline fasting glucose levels and the rate of cognitive decline in either cohort. Insulin resistance (homeostasis model assessment index) was also unrelated to cognitive function and decline.


CONCLUSIONS
Elevated fasting glucose levels and insulin resistance are not associated with worse cognitive function in older people without a history of diabetes. These data suggest either that there is a threshold for effects of dysglycemia on cognitive function or that factors other than hyperglycemia contribute to cognitive impairment in individuals with frank diabetes.
Euser
Sjoerd M
SM
Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
Sattar
Naveed
N
Witteman
Jacqueline C M
JC
Bollen
Eduard L E M
EL
Sijbrands
Eric J G
EJ
Hofman
Albert
A
Perry
Ivan J
IJ
Breteler
Monique M B
MM
Westendorp
Rudi G J
RG
D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000032:analysis; D003071:Cognition / Q000502:physiology*; D003920:Diabetes Mellitus / Q000503:physiopathology*; D005215:Fasting; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018570:Risk Assessment
D001786:Blood Glucose
Diabetes Care. 2000 Jan;23(1):57-63
10857969
J Psychiatr Res. 1975 Nov;12(3):189-98
1202204
Lancet. 2008 Jun 7;371(9628):1927-35
18501419
Am J Cardiol. 1999 Nov 15;84(10):1192-7
10569329
Arterioscler Thromb Vasc Biol. 2000 Oct;20(10):2255-60
11031212
Neurology. 2006 Sep 12;67(5):843-7
16966548
Lancet. 2002 Nov 23;360(9346):1623-30
12457784
Diabetes Care. 2003 Jan;26 Suppl 1:S5-20
12502614
Diabetes Care. 2009 Feb;32(2):221-6
19171735
Neurology. 1994 Apr;44(4):609-14
8164812
Diabetes Care. 2001 Feb;24(2):366-70
11213894
JAMA. 2004 Nov 10;292(18):2237-42
15536110
Neuroepidemiology. 2008;30(3):174-9
18421217
J Am Geriatr Soc. 2004 Oct;52(10):1713-8
15450050
Curr Alzheimer Res. 2007 Apr;4(2):147-52
17430239
Eur J Epidemiol. 2009;24(9):553-72
19728115
Diabetes Care. 1999 Dec;22(12):1988-92
10587831
Arch Intern Med. 2004 Jun 28;164(12):1327-33
15226167
Diabet Med. 2007 Jul;24(7):788-91
17403114
Neurobiol Aging. 2005 Dec;26 Suppl 1:65-9
16266773
Lancet Neurol. 2006 Jan;5(1):64-74
16361024
J Neural Transm (Vienna). 1998;105(4-5):439-61
9720973
Neurology. 1999 Dec 10;53(9):1937-42
10599761
J Neurol Neurosurg Psychiatry. 2002 Oct;73(4):385-9
12235304
J Clin Psychol. 1976 Jul;32(3):654-8
956433
Diabetes Care. 2005 Jan;28 Suppl 1:S37-42
15618111
Diabetologia. 1985 Jul;28(7):412-9
3899825