Cognition and synaptic plasticity in diabetes mellitus

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(12)60360-2.pdf

Diabetes and cognitive dysfunction.

The deleterious effects of diabetes mellitus on the retinal, renal, cardiovascular, and peripheral nervous systems are widely acknowledged. Less attention has been given to the effect of diabetes on cognitive function. Both type 1 and type 2 diabetes mellitus have been associated with reduced performance on numerous domains of cognitive function. The exact pathophysiology of cognitive dysfunction in diabetes is not completely understood, but it is likely that hyperglycemia, vascular disease, hypoglycemia, and insulin resistance play significant roles. Modalities to study the effect of diabetes on the brain have evolved over the years, including neurocognitive testing, evoked response potentials, and magnetic resonance imaging. Although much insightful research has examined cognitive dysfunction in patients with diabetes, more needs to be understood about the mechanisms and natural history of this complication in order to develop strategies for prevention and treatment.

Cognitive dysfunction and diabetes mellitus.

OBJECTIVE —To investigate the exact nature and magnitude of cognitive impairments in patients with type 1 diabetes and the possible association with other disease variables, such as recurrent episodes of hypoglycemia and metabolic control. RESEARCH DESIGN AND METHODS —MedLine and PsycLit search engines were used to identify studies on cognitive performance in patients with type 1 diabetes. Effect sizes (Cohen’s d ), which are the standardized differences between the experimental and the control group, were calculated. In the meta-analysis, a combined d value was calculated, expressing the magnitude of associations across studies. RESULTS —A total of 33 studies were identified that met the inclusion criteria. Compared with nondiabetic control subjects, the type 1 diabetic group demonstrated a significantly lowered performance on the following cognitive domains: intelligence ( d = −0.7), speed of information processing ( d = −0.3), psychomotor efficiency ( d = −0.6), visual ( d = −0.4) and sustained attention ( d = −0.3), cognitive flexibility ( d = −0.5), and visual perception ( d = −0.4). Lowered cognitive performance in diabetic patients appeared to be associated with the presence of microvascular complications but not with the occurrence of severe hypoglycemic episodes or with poor metabolic control. CONCLUSIONS —In patients with type 1 diabetes, cognitive dysfunction is characterized by a slowing of mental speed and a diminished mental flexibility, whereas learning and memory are spared.The magnitude of the cognitive deficits is mild to moderate, but even mild forms of cognitive dysfunction might hamper everyday activities since they can be expected to present problems in more demanding situations.

https://care.diabetesjournals.org/content/diacare/28/3/726.full.pdf

The Effects of Type 1 Diabetes on Cognitive Performance: A meta-analysis

Ageing and diabetes: implications for brain function

Clarification of the extent and mechanisms of damage to the central nervous system in diabetes is a frontier of current neurological research. Our aim was to obtain ample electrophysiological documentation of possible neurological abnormalities in both insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetic patients with a short duration of disease and without overt complications, taking into account metabolic control. Group 1 comprised 11 IDDM patients, and group 2 included 14 NIDDM patients treated with diet alone; the duration of disease was

Early Detection of Neurological Involvement in IDDM and NIDDM: Multimodal Evoked Potentials Versus Metabolic Control

The possible influence of diabetes on the higher mnestic and cognitive functions has been investigated. The P300 wave latency, an endogenous electrophysiological event, was explored and compared with the multimodal short-latency evoked potential (EP) recordings (visual [VEP], brainstem auditory [BAEP], and median and tibial nerve somatosensory EPs [mSEP and tSEP, respectively]) and psychometric test measures in 16 insulin-dependent diabetic (IDDM) patients, in 16 age- and (IDDM) sex-matched nondiabetic subjects, and in a large normal reference population. The age of subjects, the duration of IDDM, and the metabolic control of patients were taken into account. P300 values were significantly increased in IDDM versus matched control subjects ( P < 0.001), and 3 patients showed values above the reference value range. Abnormal VEP recordings were present in 1 of 16 patients, BAEP in 3 of 16, mSEP in 7 of 16, and tSEP in 6 of 16. Digit-span backward test results were significantly ( P < 0.02) modified in the diabetic cohort. There was no tendency for anomalies of P300, short-latency EPs, and psychometric test values to be contemporarily present, except in 1 patient. Electrophysiological or psychometric abnormalities were not clearly correlated with the duration of IDDM or the degree of short-term metabolic control. These findings give evidence that 1 ) higher cognitive functions may be affected in diabetes as documented by P300 analysis and short-term memory tests, 2 ) endogenous electrophysiological analysis highlights neuropsychological changes not detectable by psychometric tests, 3 ) an alteration of evoked potentials was present in half of the IDDM subjects studied, and 4 ) anomalies of the CNS are patchily distributed in diabetes.

Abnormalities of Cognitive Functions in IDDM Revealed by P300 Event-Related Potential Analysis: Comparison With Short-Latency Evoked Potentials and Psychometric Tests

Role of advanced glycation end-products (AGE) in late diabetic complications.

Electrophysiological alterations of the central nervous system in diabetes mellitus.

To study pupillary autonomic function in multiple sclerosis (MS), we examined 36 subjects with low disability, preserved visual acuity and no recent history (2 years) of optic neuritis or actual visual complaints. Compared to controls, MS patients showed a greater dilatator reaction with darkness and, for the light reflex, a lower amplitude and contraction rate and a greater recovery of pupillary diameter 5 s after the stimulus. Within the MS group, no difference was found comparing patients with or without the following characteristics: nuclear magnetic resonance imaging evidence of midbrain lesions; increased visual evoked potential P100 latency; and a previous history of optic neuritis. No correlation was found between P100 latency, duration of disease and pupillometric parameters. Our results indicate that in MS patients there is autonomic dysfunction with a reduction of parasympathetic tone and a relative increase in sympathetic dilatator tone to the pupils. We suggest that pupillary abnormalities could be due to non-specific impairment of the central pathways subserving pupil functions.

E. Valle

Papers

Early Detection of Neurological Involvement in IDDM and NIDDM: Multimodal Evoked Potentials Versus Metabolic Control

Abnormalities of Cognitive Functions in IDDM Revealed by P300 Event-Related Potential Analysis: Comparison With Short-Latency Evoked Potentials and Psychometric Tests

Role of advanced glycation end-products (AGE) in late diabetic complications.

Electrophysiological alterations of the central nervous system in diabetes mellitus.

Autonomic involvement in multiple sclerosis: a pupillometric study