Domain Specific Changes in Cognition at High Altitude and Its Correlation with Hyperhomocysteinemia

Though acute exposure to hypobaric hypoxia is reported to impair cognitive performance, the effects of prolonged exposure on different cognitive domains have been less studied. The present study aimed at investigating the time dependent changes in cognitive performance on prolonged stay at high altitude and its correlation with electroencephalogram (EEG) and plasma homocysteine. The study was conducted on 761 male volunteers of 25–35 years age who had never been to high altitude and baseline data pertaining to domain specific cognitive performance, EEG and homocysteine was acquired at altitude ≤240 m mean sea level (MSL). The volunteers were inducted to an altitude of 4200–4600 m MSL and longitudinal follow-ups were conducted at durations of 03, 12 and 18 months. Neuropsychological assessment was performed for mild cognitive impairment (MCI), attention, information processing rate, visuo-spatial cognition and executive functioning. Total homocysteine (tHcy), vitamin B12 and folic acid were estimated. Mini Mental State Examination (MMSE) showed temporal increase in the percentage prevalence of MCI from 8.17% on 03 months of stay at high altitude to 18.54% on 18 months of stay. Impairment in visuo-spatial executive, attention, delayed recall and procedural memory related cognitive domains were detected following prolonged stay in high altitude. Increase in alpha wave amplitude in the T3, T4 and C3 regions was observed during the follow-ups which was inversely correlated (r = −0.68) to MMSE scores. The tHcy increased proportionately with duration of stay at high altitude and was correlated with MCI. No change in vitamin B12 and folic acid was observed. Our findings suggest that cognitive impairment is progressively associated with duration of stay at high altitude and is correlated with elevated tHcy in the plasma. Moreover, progressive MCI at high altitude occurs despite acclimatization and is independent of vitamin B12 and folic acid.

[1]  C Raphel,et al.  Cognitive performance during short acclimation to severe hypoxia. , 1997, Aviation, space, and environmental medicine.

[2]  P. Brugger,et al.  Persistent cognitive impairment in climbers after repeated exposure to extreme altitude , 1989, Neurology.

[3]  C. Dufouil,et al.  Homocysteine, Folate and Cognition in a Large Community-Based Sample of Elderly People – The 3C Dijon Study , 2008, Neuroepidemiology.

[4]  C. Derouesné.  [Mini-mental state examination]. , 2001, Revue neurologique.

[5]  J. West.  Lactate during exercise at extreme altitude. , 1986, Federation proceedings.

[6]  S. Singh,et al.  Differential temporal response of hippocampus, cortex and cerebellum to hypobaric hypoxia: A biochemical approach , 2007, Neurochemistry International.

[7]  M. Lezak.  Neuropsychological assessment, 3rd ed. , 1995 .

[8]  I. Imoto,et al.  Plasma total homocysteine is associated with DNA methylation in patients with schizophrenia , 2013, Epigenetics.

[9]  E. Garrido,et al.  New evidence from magnetic resonance imaging of brain changes after climbs at extreme altitude , 2004, European Journal of Applied Physiology and Occupational Physiology.

[10]  Chiung-Chih Chang,et al.  Hyperhomocysteinemia in Alzheimer dementia patients and cognitive decline after 6 months follow-up period. , 2010, Acta neurologica Taiwanica.

[11]  R. Sacco,et al.  Total homocysteine and cognition in a tri-ethnic cohort , 2004, Neurology.

[12]  M. S. Morris.  The role of B vitamins in preventing and treating cognitive impairment and decline. , 2012, Advances in nutrition.

[13]  Ronald M. Rapee,et al.  Improving Adherence and Clinical Outcomes in Self-Guided Internet Treatment for Anxiety and Depression: Randomised Controlled Trial , 2013, PloS one.

[14]  M. Stanton,et al.  Homocysteine and cardiovascular disease , 2011 .

[15]  Halvard Stave,et al.  Recurrent Sagittal Sinus Thrombosis Occurring at High Altitude During Expeditions to Cho Oyu , 2006, Wilderness & environmental medicine.

[16]  B. Kriem,et al.  Cognitive performance during a simulated climb of Mount Everest: implications for brain function and central adaptive processes under chronic hypoxic stress , 1998, Pflügers Archiv.

[17]  Charles D. Smith,et al.  Induction of Hyperhomocysteinemia Models Vascular Dementia by Induction of Cerebral Microhemorrhages and Neuroinflammation , 2013, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[18]  R. Obeid,et al.  The role of hyperhomocysteinemia and B-vitamin deficiency in neurological and psychiatric diseases , 2007, Clinical chemistry and laboratory medicine.

[19]  L. Bender.  A VISUAL MOTOR GESTALT TEST AND ITS CLINICAL USE , 1940 .

[20]  Semra Ozdemir,et al.  The effects of chronic long-term intermittent hypobaric hypoxia on blood rheology parameters. , 2011, General physiology and biophysics.

[21]  V. Sharma,et al.  Multi-domain cognitive screening test for neuropsychological assessment for cognitive decline in acclimatized lowlanders staying at high altitude , 2012, The Indian journal of medical research.

[22]  S W Barncord,et al.  The Symbol Trail Making Test: Test Development and Utility as a Measure of Cognitive Impairment , 2001, Applied neuropsychology.

[23]  R. B. Margolis,et al.  The sensitivity of the Bender-Gestalt Test as a screening instrument for neuropsychological impairment in older adults. , 1989, The Journal of psychology.

[24]  Chao-ying Cui,et al.  Physiological Responses and Evaluation of Effects of BMI, Smoking and Drinking in High Altitude Acclimatization: A Cohort Study in Chinese Han Young Males , 2013, PloS one.

[25]  W. Selvamurthy,et al.  Effect of high altitude (HA) on event related brain potentials. , 2003, Indian journal of physiology and pharmacology.

[26]  A. Mellor,et al.  Haematological Changes at Altitude , 2011, Journal of the Royal Army Medical Corps.

[27]  P. K. Banerjee,et al.  Effect of chronic hypobaric hypoxia on components of the human event related potential. , 2004, The Indian journal of medical research.

[28]  C. Caltagirone,et al.  Reduced oxygen due to high‐altitude exposure relates to atrophy in motor‐function brain areas , 2008, European journal of neurology.

[29]  X. Weng,et al.  Minimal effects on human memory following long-term living at moderate altitude. , 2011, High altitude medicine & biology.

[30]  Colin M. Macleod.  Half a century of research on the Stroop effect: an integrative review. , 1991, Psychological bulletin.

[31]  M. Noël-Jorand,et al.  Effects of different stay durations on attentional performance during two mountain expeditions. , 2000, Aviation, space, and environmental medicine.

[32]  N. Fayed,et al.  Evidence of brain damage after high-altitude climbing by means of magnetic resonance imaging. , 2006, The American journal of medicine.

[33]  A. Beck,et al.  An inventory for measuring depression. , 1961, Archives of general psychiatry.

[34]  A. Gugliandolo,et al.  Toxic Effects of Mildly Elevated Homocysteine Concentrations in Neuronal-Like Cells , 2014, Neurochemical Research.

[35]  B Shukitt-Hale,et al.  Hypobaric hypoxia impairs spatial memory in an elevation-dependent fashion. , 1994, Behavioral and neural biology.

[36]  P. Nederkoorn,et al.  Homocysteine and cerebral small vessel disease in patients with symptomatic atherosclerotic disease. The SMART-MR study. , 2011, Atherosclerosis.

[37]  W. Sturm,et al.  Neuropsychological assessment , 2007, Journal of Neurology.

[38]  S. Karakas,et al.  Learning of serial digits leads to frontal activation in functional MR imaging. , 2006, Diagnostic and interventional radiology.

[39]  K. Shulman.  Clock‐drawing: is it the ideal cognitive screening test? , 2000, International journal of geriatric psychiatry.

[40]  J. Siuda,et al.  From mild cognitive impairment to Alzheimer's disease - influence of homocysteine, vitamin B12 and folate on cognition over time: results from one-year follow-up. , 2009, Neurologia i neurochirurgia polska.

[41]  Charles S. Houston,et al.  THE LAKE-LOUISE ACUTE MOUNTAIN-SICKNESS SCORING SYSTEM , 1993 .