1. Pilar Riobó MD, PhD
Jefe A. Endocrinología y
Nutrición.
Hospital Jiménez Díaz-Capio
Madrid. Spain.

2. Today discussion points
 Dehydration
 Exercise induced Hyponatremia
 Caloric restriccion
 N3-PUFA
 Vitamins
 Caffeine
 Physical activity and exercise

3. Decline in function resulting from dehydration

4. Role of dehydration in heat stress-induced
variations in mental performance
A battery of tests was performed to assess the effect of
various degrees of dehydration on mental performance,
n=11 soldiers of India
After 1, 2, 3, 4% dehydration induced by exercise in heat:
 Short-term memory impaired at 2% or more
dehydration
 Visual-motor tracking impaired at 2% or more
 Attention impaired at 2% or more dehydration
 Arithmetic ability impaired at 2% or more
Gopinathan PM. Arch Environ Health 43:15–17, 1988

5. Role of hydration on cognitive function
Cognitive test battery was administered prior and
30 min post- intervention (exercise or heat –
induced dehydration)
2.8% dehydration by exercise or climatic heat:
 Increased perception of fatigue
 increased tracking errors,
 increasedreaction time to making a decision,
 decreased short-term memory impaired
 Long-term memory : Impaired recall, especially
following exercise
Cian C, J Psychophysiology 14:29–36, 2000

6. Dehydration
 Performance in physical and cognitive tasks is
impaired.
 Fluid ingestion during exercise can decrease the
sensation of fatigue when exercise > 40 minutes
 A high core temperature, especially a high brain
temperature, seems to be associated with the
onset of fatigue in endurance exercise in warm
environments
 Changes in brain neurotransmiters, (dopamine)
and alterations of cerebral blood flow appear to
be responsible for fatigue when exercising in the

7. Significant dose-related effects of dehydration
Symbol substitution test effects
were observed at the 3% level
of dehydration (p < .05),
Eye-hand coordination effects
were observed at all three
levels of dehydration
Sharma VM, Sridharan K, Pichan G,
Panwar MR: Influence of heat-stress
induced dehydration on mental
functions.Ergonomics29 :791,1986

8. “How sore does your head feel now?”
“How well can you concentrate just
now?”
Changes in body mass over time for fluid
restriction and euhydration conditions
Subjects reported feelings of headache during the trial and
their ability to concentrate and their alertness were reduced.

9. Decrements in psychomotor, and
cognitive performance can occur when>
2% of body weight is lost due to water
restriction, heat, and/or physical
exertion
A major limitation of most studies
conducted to date is the inability to
determine the effects of dehydration
independent of the effects of thermal
stress, physical stress, and/or fatigue.

10. Mild dehydration impairs cognitive
performance and mood
 Randomised, single-blind, trial (N= 26)
 exercise-induced dehydration plus a diuretic
 exercise-induced dehydration plus placebo
 exercise while maintaining euhydration , plus placebo
 A cognitive test battery, mood states and symptom
questionnaire (headache, concentration and task difficulty) was
administered
Dehydration degraded aspects of cognitive performance:
 errors increased on visual vigilance
 visual working memory response latency slowed
 Fatigue and tension/anxiety increased
 Plasma osmolality increased but resting temperature was not altered
Even mild dehydration without hyperthermia
induced adverse changes in vigilance and working
memory, and increased tension/anxiety and fatigue.
Ganio, MS. Br J Nutr. 2011;106(10):1535-43

11. Today discussion points
 Dehydration
 Exercise induced Hyponatremia
 Caloric restriccion
 N3-PUFA
 Vitamins
 Caffeine
 Physcal activity and exercise

12. Exercise-associated hyponatraemia
The first reports of hyponatraemic
encephalopathy in athletes, army
personnel, and hikers appeared
shortly after the new dictum: “drink
the maximal amount that can be
tolerated”.
To date at least seven fatalities and
more than 250 cases have been
described in the medical literature.
Presumably reported cases represent
only a small proportion of all such
cases.

13. Hyponatraemic encephalopathy is a potentially life threatening
condition, with cerebral oedema causing vomiting, headache,
confusion, coma, seizures and pulmonary oedema

14. hyponatremia (Na<135 mmol/l) in 13% participants
0.6% critical hypona (<120 mmol/l).
Predictors:
• weight gain while
running
• Long racing time,
• BMI extreme

15. 1,319 collapsed runners. Hypernatremia was
present in 366 (27.7%) ; hyponatremia in 63 (4.8%).

16. Exercise-associated hyponatraemia
 Thought to be due to overconsumption of
hypotonic fluid
 inability to suppress antidiuretic hormone during
exercise or to mobilise adequate sodium from
osmotically inactive internal stores.
 Non-specific symptoms- difficult to diagnose on
site without the assistance of Na measurement,
 Any delay in treatment of patients with
encephalopathy can prove fatal.
 Mainstays of treatment include fluid restriction,
hypertonic saline, loop diuretics and mannitol.
Editorial. Overconsumption of fluids by athletes BMJ 2003;327:113-114

17. Risk factors of EAH
 military personnel,
 female
 marathon runner,
 gains weight during exercise because
 she drinks excessively
To prevent it, the advice is “ drinking
according to the personal dictates of
thirst”(fluid intake 400- 800 ml/hour)
Wijdicks EFM. Noncardiogenic pulmonary Edema in Marathon
Runners. Ann Intern Med, 2000; 133(12): 1010 - 1011.
SiegelAJ. Noncardiogenic Pulmonary Edema in Marathon
Runners. Ann Intern Med, 2000; 133(12): 1010

18. 44 years old patient admitted with serum Na 121 mmol/L &
oxigen saturation 66%
Ayus, J. C. et. al. Ann Intern Med 2000;132:711-714

19. Plasma AVP
concentrations were
markedly elevated after a
marathon despite
unchanged plasma (Na).
Pathogenesis of EAH
1. voluntary fluid intake exceeds urinary and sweat water
losses.
2. inability to maximally suppress (AVP)P during exercise
as a result of nonosmotic stimulation of AVP secretion

21. Chronic hyponatremia:
potomany associated with
eating disorders
 Overzealous correction of chronic
hyponatremia can lead to central pontine
myelinolysis, with permanent neurologic
deficits
 The initial rate of sodium correction with
hypertonic saline should not exceed 1 to 2
mmol per L per hour
 Correction of chronic hyponatremia should
be kept at a rate less than 10 mmol/L in
any 24-hour period

22. Today discussion points
 Dehydration
 Exercise induced Hyponatremia
 Caloric restriccion
 N3-PUFA
 Vitamins
 Caffeine
 Physcal activity and exercise

23. Healthy elderly subjects, 3 groups:
1. caloric restriction (30% reduction)
2. increased intake of UFAs (20%, unchanged total
fat),
3. control
Before and after 3 months of intervention, memory
was assessed under standardized conditions.
Witte A V et al. PNAS 2009;106:1255-1260

24. Percentage changes in weight, BMI , and unsaturated-to-saturated
fatty acids ratio after caloric restriction (group 1),
UFA enhancement (group 2), and control condition.
Witte A V et al. PNAS 2009;106:1255-1260

25. Significant increase in verbal memory scores after caloric
restriction (mean 20%), which was correlated with
decreases in plasma levels of insulin and CRP
Mechanisms: higher synaptic plasticity and stimulation of
neurofacilitatory pathways in the brain because of improved
insulin sensitivity and reduced inflammation

26. Beneficial effect of CR or
RSV supplementation on
specific cognitive functions
in a primate.
RSV could be a good
candidate to mimic long-
term CR effects

27. Cognition
Leptin ?
Caloric restriccion longevity

28. Today discussion points
 Dehydration
 Exercise induced Hyponatremia
 Caloric restriccion
 N3-PUFA
 Vitamins
 Caffeine
 Physcal activity and exercise

29. Evidence has accumulated suggesting that the
beneficial effect of fish is due to its content in omega-
3 polyunsaturated fatty acids (n-3 PUFAs)
2 kinds of omega-3 fatty acids:
plant-derived (α-linolenic acid) and
marine-derived (eicosapentaenoic acid [EPA] and
docosahexaenoic acid [DHA])

30. N-3 polyunsaturated fatty acids (PUFA)
1. α-linolenic acid: long-chain, 18-carbon atom with 3
double bonds
2. Eicosapentaenoic acid (EPA): 20 carbon atoms and
5 double bonds
3. Docosahexaenoic acid (DHA): 22 carbon atoms
and 6 double bonds
n-3 PUFA are "essential“: we cannot make them in our
bodies and they are needed for normal growth,
development, and optimal function of brain, heart, and
other systems

31. N3-PUFA
 Important during early brain development, with low intake
resulting in poor neurological development and low IQ
(Innis SM. Dietary omega 3 fatty acids and the developing brain. Brain
Res. 2008;1237:35–43)
 Such associations may extend through adolescence
(Aberg MA. Fish intake of Swedish male adolescents is a predictor of
cognitive performance. Acta Paediatr. 2009;98:555–60).
 In late life, low fish intake predicts greater age-related
cognitive dysfunction and elevated risk for Alzheimer's
dementia
(Morris MC. Fish consumption and cognitive decline with age in a large
community study. Arch Neurol. 2005;62:1849–53)

32. 280 volunteers, 35 - 54 y.o.
Distributed by quintiles of DHA
intake
Higher DHA (mol %) was
related to better performance
on tests of nonverbal
reasoning and mental
flexibility, working memory,
and vocabulary (P ≤ 0.05).
Muldoon MF. Serum phospholipid docosahexaenonic acid is associated with
cognitive functioning during middle adulthood. J Nutr. 2010;140(4):848-53.

33. Chicago Health and Aging Project
Annual rate of change in cognitive score
(standardized units per year [SU/y])
by number of fish meals per week 3718 persons , > 65 years:
•cognitive testing were
conducted (basal & 3 years)
• self-administered food frequency
questionnaire (FFQ)
were conducted (basal & 3 years)
Fish consumption may
be associated with
slower cognitive decline
with age
Morris, M. C. et al. Arch Neurol 2005;62:1849-1853.

34. DHA May Prevent Age-Related Dementia
DHA acts at multiple steps to
reduce the production of the β-
amyloid
1. moderates some of the
kinases that
hyperphosphorylate the τ-
protein, a component of the
neurofibrillary tangle.
2. help suppress
neuroinflammation, and
oxidative damage that
contribute to synaptic loss and
neuronal dysfunction
3. increases brain levels of
neuroprotective brain-derived
neurotrophic factor
AD pathways targeted by DHA.
Cole G M , Frautschy S A J. Nutr. 2010;140:869

35. Today discussion points
 Dehydration
 Exercise induced Hyponatremia
 Caloric restriccion
 N3-PUFA
 Vitamins
 Caffeine
 Physcal activity and exercise

36. Hyperhomocystenemia
and B12 deficiency
 Evidence is convincing that hyperhomocysteinemia
is a risk factor for dementia (leukoaraiosis )
 B12 deficiency manifestations include abnormal
psychiatric, neurological, gastrointestinal, and
hematological findings (pernicious anemia)
 Subclinical deficiencies exit (metformin¡¡)
 Assessing serum B12 : <200 pg/ml
 Patients with B12 deficiency and mild cognitive
impairment or dementia, might show cognitive
improvement with supplemental B12 treatment.

37. SAM
Aceptor ATP
Receptor Metionina
Ser
SAHomocis
THF
Aden Gly
Homocys metilen THF
B12
B6
Ser metil THF
Cistationina
B6
K-butirato Cys

38. Folic Acid
 Low levels of folate are associated with
high blood levels of homocysteine which
has been linked with the risk of arterial
disease, dementia and Alzheimer's disease
 long-term folic acid supplements appear to
improve cognitive function of healthy older
people with high homocysteine levels
 There is a risk that folate supplementation
can delay the diagnosis of B12 deficiency,
which can cause irreversible neurological
damage. So, folic acid supplementation
must associate vitamin B12

39. Today discussion points
 Dehydration
 Exercise induced Hyponatremia
 Caloric restriccion
 N3-PUFA
 Vitamins
 Caffeine
 Physical activity and exercise

40. A case-control study
Cases were 54 patients with probable AD
Controls ,54 persons, cognitively normal, matched
Patients with AD had an average daily caffeine
intake of 73 mg during the 20 years that preceded
diagnosis of AD, whereas the controls had an
average daily caffeine intake of 198.7 +/- 135.7 mg
Caffeine intake was associated with a
significantly lower risk for AD, independently
of other possible confounding variables
Maia & de Mendonça. Eur J Neurol 2002 9:377

41. Cardiovascular Risk, Aging and Dementia
(CAIDE Study)
After an average follow-up of 21 years, 1409 individuals
(71%) aged 65 to 79 completed the re-examination in 1998.
A total of 61 cases were identified as demented
Coffee drinkers at midlife had lower risk of dementia and AD
later in life adjusted for demographic, lifestyle and vascular
factors, apolipoprotein E epsilon4 allele and depression
The lowest risk (65% decreased) was found in people who
drank 3-5 cups per day.
Coffee drinking at midlife is associated with a decreased risk of
dementia/AD later in life. This finding might open possibilities
for prevention of dementia/AD
Eskelinen, M et al. Midlife Coffee and Tea Drinking and the Risk of
Late-Life Dementia: A Population-Based CAIDE Study . J Alzheimer Dis 16 (2009) 85-91

42. Caffeine
Epidemiological studies have found an association between
coffee consumption and improved cognitive function in AD
patients and in the elderly.
Long-term administration of caffeine (non-selective adenosine
antagonist) in animals showed a reduced amyloid burden in
brain with better cognitive performance.
Adenosine receptors play important roles in the modulation of
cognitive function. Antagonists of adenosine A2A receptors
mimic the beneficial effects of caffeine on cognitive function.
The adenosinergic system constitutes a new therapeutic target
for AD, and caffeine and A2A receptor antagonists may have
promise to manage cognitive dysfunction in AD

43. Today discussion points
 Dehydration
 Exercise induced Hyponatremia
 Caloric restriccion
 N3-PUFA
 Vitamins
 Caffeine
 Physical activity and exercise

44. Mean Differences in Change in Cognitive
Function Scores by Quintile of Physical Activity*.
higher levels of physical activity, including
walking, are associated with better cognitive
function and less cognitive decline
Weuve, J. et al. JAMA 2004;292:1454-1461

45. Clear and strong associations between greater physical activity
and reduced cognitive decline in women with vascular disease
Adjusted global cognition composite score during the cognitive follow-up period (1998-2005) by
quintile of total physical activity at baseline (n = 2809)
Vercambre, M.-N. et al. Arch Intern Med 2011;171:1244-1250.

46. AEE as 90% of total energy Cognitive function was assessed at
expenditure (assessed using doubly baseline and 2 or 5 years later
labeled water) minus resting metabolic using the Modified Mini-Mental
rate (measured using calorimetry) State Examination
In this study, older adults with higher objectively
measured total daily activity had a lower incidence
of cognitive impairment

47. PRCT, randomized to a high-intensity aerobic exercise (45 to 60 min/d, 4 d/wk for 6
months) vs control. Results Six months of high-intensity aerobic exercise had effects on
cognition
Mean values representing the change from baseline for cognitive measures
Baker, L. D. et al. Arch Neurol 2010;67:71-79.

48. These studies showed that systematized
physical activity contributed to at least
improve temporarily some cognitive
functions of patients with Alzheimer's
disease, particularly, attention, executive
functions and language
Coelho et al. Rev Bras Psiquiatr.2009 ;31(2):163-70.

49. Thank you very much for
your attention