Relationship between Cognitive Function, Growth Hormone and Insulin-Like Growth Factor I Plasma Levels in Aged Subjects

Basal growth hormone (GH) and insulin-like growth factor I (IGF-I) as well as GH responses to GH-releasing hormone (GHRH) were studied in 22 subjects (7 females, 15 males), aged between 65 and 86 years. The study was aimed at investigating the possible correlations between the age-dependent GH-IGF-I axis decline and the cognitive function – assessed by the Mini Mental State Examination (MMSE). The relationship between hormonal data, cognition and age, body weight, body mass index (BMI), some nutritional indices (triceps skinfolds, TSF, mid-arm circumference, MAC), and physical activity – quantified by the physical functioning index (PFI) – were also analyzed. GH basal levels were within the normal range, while GH responses to GHRH were blunted in most cases. GH peaks after GHRH were directly correlated with GH basal values. IGF-I serum levels were found to be in the lower part of the reference range for adult subjects or below it. GH responses to GHRH, but not GH and IGF-I basal levels, were inversely correlated with subject age. GH secretion areas after GHRH were inversely correlated with BMI, but no further correlations between GH data and clinical or nutritional parameters were found. MMSE values directly correlated with MAC and PFI values. IGF-I levels were directly correlated with MMSE scores, being lowered in patients with more advanced cognitive deterioration, and with MAC values – the decrease of which is thought to reflect protein caloric malnutrition – but not with body weight, BMI, TSF and PFI. MMSE-related protein caloric malnutrition and decreased physical activity possibly take part in affecting IGF- I function in subjects with mild cognitive impairment and, reciprocally, IGF-I decrement might affect neuronal function.

[1]  M. Vitiello,et al.  Somatomedin-C levels in healthy young and old men: relationship to peak and 24-hour integrated levels of growth hormone. , 1985, Journal of gerontology.

[2]  M. Gunning,et al.  The Effects of IGF-1 Treatment after Hypoxic-Ischemic Brain Injury in Adult Rats , 1993, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[3]  D. Clemmons,et al.  Dietary components that regulate serum somatomedin-C concentrations in humans. , 1983, The Journal of clinical investigation.

[4]  H. Roffwarg,et al.  Age-related change in the twenty-four-hour spontaneous secretion of growth hormone. , 1972, The Journal of clinical endocrinology and metabolism.

[5]  M. Rodríguez-Arnao,et al.  GHRH-induced GH response in patients with senile dementia of the Alzheimer type. , 1988, Acta endocrinologica.

[6]  A. Shetter,et al.  Cortical biopsy in Alzheimer's disease: Diagnostic accuracy and neurochemical, neuropathological, and cognitive correlations , 1992 .

[7]  G. Solinas,et al.  Effects of pyridostigmine, corticotropin-releasing hormone and growth hormone-releasing hormone on the pituitary-adrenal axis and on growth hormone secretion in dementia. , 1993, Neuropsychobiology.

[8]  M. Viitanen,et al.  Insulin-like growth factors and insulin-like growth factor binding proteins in cerebrospinal fluid and serum of patients with dementia of the Alzheimer type , 1993, Journal of neural transmission. Parkinson's disease and dementia section.

[9]  M. Esiri,et al.  Alzheimer's disease Correlation of cortical choline acetyltransferase activity with the severity of dementia and histological abnormalities , 1982, Journal of the Neurological Sciences.

[10]  R. Wiswell,et al.  Age-dependent effect of resistance exercise on growth hormone secretion in people. , 1992, The Journal of clinical endocrinology and metabolism.

[11]  M. Blackman,et al.  Continuous subcutaneous infusions of growth hormone (GH) releasing hormone 1-44 for 14 days increase GH and insulin-like growth factor-I levels in old men. , 1993, The Journal of clinical endocrinology and metabolism.

[12]  James M. Bower,et al.  Acetylcholine and memory , 1993, Trends in Neurosciences.

[13]  D. Clemmons,et al.  6 Factors controlling blood concentration of somatomedin C , 1984 .

[14]  Obert,et al.  Effects of human growth hormone in men over 60 years old. , 1990, The New England journal of medicine.

[15]  M. Blackman,et al.  Growth hormone (GH)-releasing hormone-(1-29) twice daily reverses the decreased GH and insulin-like growth factor-I levels in old men. , 1992, The Journal of clinical endocrinology and metabolism.

[16]  V. Mitev,et al.  [Insulin-like growth factors]. , 1990, Eksperimentalna meditsina i morfologiia.

[17]  GROWTH HORMONE SECRETION IN PRIMARY DEGENERATIVE DEMENTIA: CORRELATIONS WITH COGNITIVE IMPAIRMENT , 1996 .

[18]  E. Parati,et al.  Growth Hormone Responses to Cholinergically Active Drugs in Patients with Dementia of the Alzheimer Type , 1992, Alzheimer disease and associated disorders.

[19]  A. Rogol,et al.  Effects of sex and age on the 24-hour profile of growth hormone secretion in man: importance of endogenous estradiol concentrations. , 1987, The Journal of clinical endocrinology and metabolism.

[20]  J. Ketelslegers,et al.  Nutritional regulation of the insulin-like growth factors. , 1994, Endocrine reviews.

[21]  R. McCARTER,et al.  The influence of age on the 24-hour integrated concentration of growth hormone in normal individuals. , 1985, The Journal of clinical endocrinology and metabolism.

[22]  G. Wolf-Klein,et al.  Weight Loss in Alzheimer's Disease: An International Review of the Literature , 1994, International Psychogeriatrics.

[23]  R. Marcus,et al.  The effects of recombinant human insulin-like growth factor-I and growth hormone on body composition in elderly women. , 1995, The Journal of clinical endocrinology and metabolism.

[24]  M. Kutner,et al.  Impaired growth hormone secretion in the adult population: relation to age and adiposity. , 1981, The Journal of clinical investigation.

[25]  W. Daughaday,et al.  Inhibition of access of bound somatomedin to membrane receptor and immunobinding sites: a comparison of radioreceptor and radioimmunoassay of somatomedin in native and acid-ethanol-extracted serum. , 1980, The Journal of clinical endocrinology and metabolism.

[26]  A. Vermeulen.  Nyctohemeral growth hormone profiles in young and aged men: correlation with somatomedin-C levels. , 1987, The Journal of clinical endocrinology and metabolism.

[27]  E K Perry,et al.  Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. , 1978, British medical journal.

[28]  P. Monteleone,et al.  Repetitive growth hormone-releasing hormone administration restores the attenuated growth hormone (GH) response to GH-releasing hormone testing in normal aging. , 1989, The Journal of clinical endocrinology and metabolism.

[29]  M. Blackman,et al.  Human growth hormone and human aging. , 1993, Endocrine reviews.

[30]  C. Benbassat,et al.  Circulating levels of insulin-like growth factor (IGF) binding protein-1 and -3 in aging men: relationships to insulin, glucose, IGF, and dehydroepiandrosterone sulfate levels and anthropometric measures. , 1997, The Journal of clinical endocrinology and metabolism.

[31]  P. Hindmarsh,et al.  Peak and trough growth hormone concentrations have different associations with the insulin-like growth factor axis, body composition, and metabolic parameters. , 1997, The Journal of clinical endocrinology and metabolism.

[32]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[33]  M. Mattson,et al.  IGF-I and IGF-II protect cultured hippocampal and septal neurons against calcium-mediated hypoglycemic damage , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[34]  F Savoldi,et al.  Cholinergic modulation of growth hormone-releasing hormone effects on growth hormone secretion in dementia. , 1990, Neuropsychobiology.

[35]  E. Arvat,et al.  Neural Control of Growth Hormone Secretion in Aged Humans , 1993 .

[36]  D. Clemmons,et al.  Factors controlling blood concentration of somatomedin C. , 1984, Clinics in endocrinology and metabolism.

[37]  M. Kerkhofs,et al.  Neuroendocrine rhythms and sleep in aging men. , 1991, The American journal of physiology.

[38]  M. Franceschi,et al.  Growth hormone secretion in Alzheimer's disease: studies with growth hormone-releasing hormone alone and combined with pyridostigmine or arginine. , 1993, Dementia.

[39]  D. Cocchi,et al.  Growth Hormone and Somatomedins during Lifespan , 1993, Springer Berlin Heidelberg.

[40]  K. Krishnan,et al.  Growth hormone response to growth hormone releasing factor in Alzheimer's disease. , 1989, Neuroendocrinology.

[41]  B. Craig,et al.  Effects of progressive resistance training on growth hormone and testosterone levels in young and elderly subjects , 1989, Mechanisms of Ageing and Development.

[42]  D. Le Roith,et al.  Seminars in medicine of the Beth Israel Deaconess Medical Center. Insulin-like growth factors. , 1997 .

[43]  J. Cabranes,et al.  Cholinergic mediation of growth hormone secretion elicited by arginine, clonidine, and physical exercise in man. , 1984, The Journal of clinical endocrinology and metabolism.

[44]  G. Paolisso,et al.  Serum levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in healthy centenarians: relationship with plasma leptin and lipid concentrations, insulin action, and cognitive function. , 1997, The Journal of clinical endocrinology and metabolism.

[45]  E. Poehlman,et al.  Influence of physical activity on insulin-like growth factor-I in healthy younger and older men. , 1990, The Journal of clinical endocrinology and metabolism.