Higher Normal-Range Blood Sugar Is Linked to Lower Memory Performance and Smaller Hippocampus

New research shows that even people without diabetes or pre-diabetes who have higher blood sugar values within the normal range tend to perform worse on memory tests and to have smaller hippocampal volumes.

Study overview

A study published in the journal Neurology examined 141 adults with an average age of 63 who did not meet diagnostic criteria for diabetes or impaired glucose tolerance (pre-diabetes). The researchers deliberately excluded individuals who were overweight, who reported drinking more than three and a half alcoholic drinks per day, and those who already showed clinically detectable memory or thinking impairments. By studying a relatively healthy group, the investigators aimed to isolate the relationship between blood glucose levels within the normal range and brain health.

How the research was conducted

Participants completed standardized memory assessments and had blood tests to measure average blood glucose control, including the long-term marker HbA1c. In addition, all participants underwent brain imaging with MRI to measure the size and microstructure of the hippocampus, a brain region centrally involved in forming and retrieving memories. The combination of cognitive testing, laboratory measurement, and structural brain imaging allowed the team to examine associations among blood sugar, memory performance, and hippocampal anatomy.

Key findings

The investigators found consistent associations between higher blood glucose markers and poorer memory. On a delayed recall test—where participants were asked to remember a list of 15 words thirty minutes after hearing them—individuals with higher blood glucose remembered fewer words. Quantitatively, the study reports that an increase of about 7 mmol/mol in HbA1c, a marker of long-term glucose control, corresponded with recalling approximately two fewer words on that delayed recall test. In addition to the cognitive differences, higher glucose measures were associated with smaller hippocampal volumes on MRI.

Interpretation and implications

These results suggest that even modest elevations in blood glucose within the range considered normal may relate to measurable differences in memory and to structural characteristics of the hippocampus. The findings support the idea that brain health and cognitive aging are influenced not only by clinically diagnosed diabetes but also by variations in glucose regulation that fall short of diabetic thresholds. Because the hippocampus plays a vital role in memory encoding and retrieval, smaller hippocampal volume could partially explain the link between higher glucose and poorer recall.

The study’s lead author, Agnes Flöel, MD, of Charité University Medicine in Berlin, emphasized that lowering blood glucose—even for people who are not diabetic—might be a promising avenue for preventing age-related cognitive decline. Suggested approaches for reducing glucose levels include dietary changes to lower caloric intake and increased physical activity, both of which are established strategies to improve metabolic health and may carry cognitive benefits.

Limitations and next steps

As an observational study, the research identifies associations but does not prove causation. The sample excluded people with obesity, heavy alcohol use, or existing cognitive impairment, which strengthens the focus on normal-range glucose but may limit generalizability to broader populations. Further research, including prospective and intervention studies, is needed to determine whether reducing blood glucose within the normal range can directly preserve memory and hippocampal structure over time.

Funding and disclosures

The research was supported by the German Research Foundation, the Else Kröner-Fresenius Foundation, and the German Ministry of Education and Research.

Sources and citation

Press contact: Rachel Seroka – AAN
Source: AAN press release
Image credit: Amber Rieder and Jenna Traynor (public domain)
Original research: “Higher glucose levels associated with lower memory and reduced hippocampal microstructure” by Lucia Kerti, MA; A. Veronica Witte, PhD; Angela Winkler, MA; Ulrike Grittner, PhD; Dan Rujescu, MD; and Agnes Flöel, MD. Published online October 23, 2013 in Neurology. DOI: 10.1212/01.wnl.0000435561.00234.ee

Keywords: blood sugar, glucose, HbA1c, memory, hippocampus, cognitive decline, aging, metabolic health