Insulin inhaled via a nasal spray may slow decline in cognitive function in people with Alzheimer’s disease and amnestic mild cognitive impairment, a condition thought to precede Alzheimer’s, according to the results of a pilot study published online first in the Archives of Neurology on Monday.

Insulin plays a number of roles in the central nervous system, and research shows insulin levels and insulin activity are lower in the central nervous system of patients with Alzheimer’s.

Previous studies have shown that insulin dysregulation in the brain appears to contribute to the development of Alzheimer’s disease, which in its earliest stages is marked by synaptic loss and memory impairment. Synaptic loss is where the connections between brain cells or neurons are destroyed.

More specifically, some animal studies have shown insulin may prevent synaptic loss and reduce deposits of Aβ, the main component of amyloid plaques that is found in the brains of people with Alzheimer’s disease.

In the light of this, it has been suggested that restoring insulin levels to normal in patients with Alzheimer’s might protect cognitive ability, hence the reason for this study.

In their randomized, controlled trial, Dr Suzanne Craft of the Veterans Affairs Puget Sound Health Care System and the University of Washington School of Medicine, Seattle, USA, and colleagues, evaluated the effects of intranasal insulin therapy on patients with amnestic mild cognitive impairment or Alzheimer’s disease.

They randomly assigned 104 participants to three study groups. The average age of the participants was 72, and more than half were men. 64 of them had amnestic mild cognitive impairment, and 40 had mild to moderate Alzheimer’s disease.

For four months, 36 participants received 20 International Units (IUs) of insulin a day, 38 received 40 IUs a day, and 30 received a daily placebo, all delivered via nasal spray.

The researchers looked at the effect of the treatment on cognition, daily function, and for some participants, they measured biomarkers of cerebral glucose metabolism and cerebrospinal fluid.

The primary measures were delayed story recall (how well participants recalled a story told to them immediately after and a short time after being told it), and Dementia Severity Rating Scale (DSRS) scores of the participants (a multiple choice questionnaire that is filled in by caregivers).

The researchers also took secondary measures, including one that assesses cognitive ability (the ADAS-cog scale) and one that assesses activities of daily living in people with Alzheimer’s (ADCS-ADL scale).

For the biomarkers, 23 of the participants underwent lumbar puncture and 40 underwent positron emission tomography (PET) assessment with fludeoxyglucose F 18 (a measure of glucose metabolism) before and after treatment.

For the primary measures, the results showed that compared to the placebo group:

  * The participants who took 20 IUs of insulin a day showed improved delayed story recall (P<.05).

* However, there was no improvement for the participants who took 40 IUs of insulin a day.

* The DSRS caregiver-rated functional ability was maintained for the insulin groups (P<.01).

For the secondary measures, the authors note that:

"Both insulin doses also preserved general cognition as assessed by the ADAS-cog score for younger participants and functional abilities as assessed by the ADCS-ADL scale for adults with AD (P < .05)."

Although there appeared to be no change in cerebrospinal fluid biomarkers for insulin-treated participants as a group, exploratory analyses showed changes in memory and function were linked to changes in the Aβ42 level, and in the tau protein to Aβ42 ratio in cerebrospinal fluid.

The PET imaging showed that the participants on placebo had decreased fludeoxyglucose F 18 uptake (suggesting poorer glucose metabolism) in some brain regions, such as the parietotemporal, frontal, precuneus, and cuneus.

No serious treatment-related adverse events occurred during the study.

In their discussion, the authors suggest the reason only the lower insulin dose appeared to make a positive difference to the story recall measure could be because in previous research they had seen an upside-down U-shaped curve for this treatment, with negative effects occurring at too low and too high levels of insulin.

They conclude that:

"... the results of our pilot trial demonstrate that the administration of intranasal insulin stabilized or improved cognition, function and cerebral glucose metabolism for adults with aMCI [amnestic mild cognitive impairment] or AD [Alzheimer's Disease]."

"Taken together, these results provide an impetus for future clinical trials of intranasal insulin therapy and for further mechanistic studies of insulin's role in the pathogenesis of AD," they add.

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Written by Catharine Paddock PhD
Medical News Today