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Pilar Riobó MD, PhD
Jefe A. Endocrinología y
Nutrición.
Hospital Jiménez Díaz-Capio
Madrid. Spain.
Today discussion points
  Dehydration
  Exercise induced Hyponatremia
  Caloric restriccion
  N3-PUFA
  Vitamins
  Caffeine
  Physical activity and exercise
Decline in function resulting from dehydration
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
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
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
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
“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.
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.
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
Today discussion points
 Dehydration
 Exercise induced Hyponatremia
 Caloric restriccion
 N3-PUFA
 Vitamins
 Caffeine
 Physcal activity and exercise
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.
Hyponatraemic encephalopathy is a potentially life threatening
condition, with cerebral oedema causing vomiting, headache,
confusion, coma, seizures and pulmonary oedema
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
1,319 collapsed runners. Hypernatremia was
present in 366 (27.7%) ; hyponatremia in 63 (4.8%).
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
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
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
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
Diet and mental performance
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
Today discussion points
 Dehydration
 Exercise induced Hyponatremia
 Caloric restriccion
 N3-PUFA
 Vitamins
 Caffeine
 Physcal activity and exercise
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
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
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
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
Cognition


             Leptin ?

Caloric restriccion      longevity
Today discussion points
 Dehydration
 Exercise  induced Hyponatremia
 Caloric restriccion
 N3-PUFA
 Vitamins
 Caffeine
 Physcal activity and exercise
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])
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
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)
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.
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.
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
Today discussion points
 Dehydration
 Exercise  induced Hyponatremia
 Caloric restriccion
 N3-PUFA
 Vitamins
 Caffeine
 Physcal activity and exercise
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.
SAM
    Aceptor                      ATP

Receptor                     Metionina
                                                      Ser
   SAHomocis
                                         THF

           Aden                                             Gly
                       Homocys               metilen THF
                                       B12
                  B6
   Ser                                 metil THF
                   Cistationina
                   B6


           K-butirato            Cys
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
Today discussion points
 Dehydration
 Exercise  induced Hyponatremia
 Caloric restriccion
 N3-PUFA
 Vitamins
 Caffeine
 Physical activity and exercise
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
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
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
Today discussion points
 Dehydration
 Exercise  induced Hyponatremia
 Caloric restriccion
 N3-PUFA
 Vitamins
 Caffeine
 Physical activity and exercise
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
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.
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
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.
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.
Thank you very much for
     your attention

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Diet and mental performance

  • 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