What is the optimal blood glucose range for maintaining normal brain function in adults, and what targets are recommended for non‑diabetic versus diabetic individuals?

Optimal Blood Glucose for Brain Function

For non-diabetic adults, maintain fasting blood glucose ≤6.1 mmol/L (≤110 mg/dL) to preserve brain structure and cognitive function, while for diabetic adults, target A1C <7.0-7.5% (fasting 80-130 mg/dL) if healthy, but prioritize strict avoidance of hypoglycemia over tight control in those with cognitive impairment or multiple comorbidities.

Non-Diabetic Adults: The Lower the Better (Within Normal Range)

Blood glucose levels even in the "normal" range significantly impact brain health. Higher glucose within the normal range (<6.1 mmol/L) is associated with:

• Greater brain atrophy in frontal cortices (middle frontal gyrus, inferior frontal gyrus, precentral gyrus), hippocampus, and amygdala in cognitively healthy older adults 1
• Poorer cognitive performance, particularly in men, with structure-function associations showing gender-specific vulnerability 1
• Localized glucose hypometabolism (11-17% lower) in superior frontal cortex, caudal middle frontal cortex, and caudate in older adults, even when cognitively normal 2

The critical threshold appears to be 6.1 mmol/L (110 mg/dL). Above this level, even in non-diabetics, there is increased risk of cognitive decline 3. This challenges conventional definitions of "normal" glucose and suggests that optimal brain health requires glucose levels at the lower end of the normal range 1.

Diabetic Adults: A Delicate Balance

Healthy Diabetic Adults (Intact Cognition, Few Comorbidities)

Target A1C <7.0-7.5% (53-58 mmol/mol) with time in range 70-180 mg/dL of ≥70% and time below range <70 mg/dL of <4% 4. This translates to:

• Fasting/preprandial glucose: 80-130 mg/dL (4.4-7.2 mmol/L) 4
• Bedtime glucose: 80-180 mg/dL (4.4-10.0 mmol/L) 4

The rationale: These individuals have longer life expectancy and can benefit from tighter control without excessive hypoglycemia risk 4.

Diabetic Adults with Cognitive Impairment or Multiple Comorbidities

Target A1C <8.0% (64 mmol/mol) with time in range of ≥50% and time below range <1% 4. This translates to:

• Fasting/preprandial glucose: 90-150 mg/dL (5.0-8.3 mmol/L) 4
• Bedtime glucose: 100-180 mg/dL (5.6-10.0 mmol/L) 4

Hypoglycemia avoidance takes absolute priority over tight glycemic control 4, 5. The evidence is clear:

• Severe hypoglycemia increases dementia risk in older adults with type 2 diabetes 5
• Cognitive impairment and hypoglycemia create a vicious bidirectional cycle—each worsens the other 5
• Prolonged neuroglycopenia (>2 hours) causes permanent or fatal brain injury 5

Very Complex/Poor Health Diabetic Adults

Avoid reliance on A1C targets; focus exclusively on preventing hypoglycemia (<100 mg/dL) and symptomatic hyperglycemia (>200 mg/dL) 4. Target glucose range: 100-200 mg/dL (5.6-11.1 mmol/L) 4.

The Hypoglycemia Danger Zone

Blood glucose <70 mg/dL (3.9 mmol/L) impairs executive function with large effect sizes in both diabetic and non-diabetic adults 6. Executive functions—which govern organization, prioritization, and time management—are significantly impaired during hypoglycemia, with:

• Lower test scores and increased time required for task completion 6
• More severe impairment in adults with diabetes compared to those without 6
• Permanent brain injury risk if hypoglycemia persists >2 hours 5

Hyperglycemia and Brain Function

In diabetic adults, each 1 mmol/L increment in fasting blood glucose increases dementia risk (adjusted HR 1.51,95% CI 1.25-1.82) 3. Higher HbA1c is specifically associated with:

• Poorer executive function performance in cognitively impaired older adults (beta = -4.37, p = 0.001) 7
• Faster annual decline in MMSE scores among diabetic participants (β = 0.10, p = 0.0018) 3
• 73% increased risk of all-cause dementia, 56% increased risk of Alzheimer disease, and 127% increased risk of vascular dementia 5

Critical Clinical Pitfalls

The ACCORD-MIND trial demonstrated that intensive glucose control does not benefit brain structure or cognitive function 4. This finding is crucial: overly aggressive glucose lowering causes more harm than benefit through recurrent hypoglycemia 4.

Screen annually for impaired hypoglycemia awareness using validated questionnaires or by asking if patients experience low glucose without symptoms 5. Patients with hypoglycemia unawareness should have glycemic targets raised to strictly avoid further hypoglycemia for several weeks 5.

Consider continuous glucose monitoring (CGM), which reduces hypoglycemia time by approximately 27 minutes daily in older adults 5. CGM provides superior assessment with time in range, time above range, and time below range metrics 8.

Screen annually for cognitive impairment in adults ≥65 years using Mini-Mental State Examination, Mini-Cog, or Montreal Cognitive Assessment 5. Cognitive decline necessitates immediate relaxation of glycemic targets to prevent the hypoglycemia-dementia cycle 5.