PREVENTION

Ten percent of persons older than 65,
50% of those older than 85 years have AD

Early pathological changes

  • depositation of beta amyloid (A B 42)
  • related tau accumulation

APP generates beta amyloid rangin from 39 to 42 aminoacid peptide

Later pathological changes

  • AB 42 and TAU aggregates progress to plaques e tangles widespread in the brain
  • synaptic dysfunction
  • neuronal loss
  • degeneration of some regions due to neurotransmitter deficit: degeneration on basal forebrain is associated with decrements in acetylcholine-mediated neuronal activity involved in memory

AD risk factor

  • Genetic
  • clinical
  • environmental
  • vascular (diabetes mellitus, hypertension, dyslipidemia, smoking)

prophilaxes

  • primary: avoidance of age-related decline
  • secondary: prevention or slowing progression MCI to dementia
  • tertiary: treatment of dementia
  • AB and tau aggregation inhibitors
  • antioxidants
  • anti-inflammatory compounds
  • cognitive enhancers or facilitators
  • neuroprotective agents
  • pleiotropic interventions

Vitamins e Minerals

B1 vitamin (Thiamine) exist in

  • grain cereals
  • orhan meats
  • milk
  • vegetables

Low thiamine diet causes

  • impaired cognitive performance
  • brain damage
  • blood-brain barrier dysfunction
  • intracellular edema
    High thiamine
  • improvement in ADAS (AD scale)
  • scores in MMSE
  • Low is not asociated to AD

B2 vitamin (ribofralin) is in the same products as B1

  • improve cognitive performance
  • better MMSE
  • low B2 is not associated to AD

B6 vitamin (pyridoxine) e B12 (cobalamin) come from meat, poultry, seafood, eggs, cereals

Low B6

  • worst motor skills
    high dose improve LTM
  • Low associated with AD

Low B12 associated to faster rate of cognitive decline, especially in APOEe4 carries.
It causes a reversible cause of dementia

Folates (B9)

  • green leafe vegetables: spinach, parsley, romaine lettuce,
  • asparagus, cauliflower, broccoli, beets
  • legumes

Folate supplemention

  • improves cognitive scores in aged patients with cognitive impairment
  • improve cognition in O
  • in mices APOE-deficient, idecrement in the amount of oxidative = mices getting well
  • high folate dietary protects against cognitive decline

Folate deficience

  • In CA3 20% fewer neurons

B12, B6, Folate are antioxydant e antiinflammatory. they interact in the metabolism of homocysteine
It's neurotoxic and it's a risk factor for vascular desease and dementia

Vitamin C e E

  • powerful antioxidant
  • better cognitive performance with vitamin C
  • high C e E higher MMSE scores
  • Low lower MMSE scores

Chromium

It's a trace mineral used in insulin receptor signal. It amplify insulin signal
Chromium supplementation increases activation in thalamus e frontal cortex

Polyphenolic compounds -Flavonoids

  • wine related myricetin
  • curcumin
  • nordihydroguaiaretic acid (NDGA)
  • rosmarinic acid (RA)
    antioxidative, antiviral, anticarcinogenic
    strong anti AB aggregation

Berries:

  • against oxidative e inflammatory processes
  • improve cognitive performance, increase neurogenesis in dentate

Curcumin:

  • antioxidant
  • inhibit ab oligomers and fibrils

Omega-3

  • polyunsatured fatty acid
  • in marine algae, fatty fish, fish oil
  • pleiotropic mechanism
  • antiinflammatory activity, neuroprotection, neurogenesis, antioxidant, metabolic enhancer
  • prevention on cognitive decline in APOEe4 patients

Diet

Mediterranean diet associated with better cognition

Other supplements

Garlic

  • reduce cardiovascular risk factors and their impact on developing AD
  • antioxidant
  • reduce homocysteine

Ginko Biloba

  • antiinflammatory e antioxidant
  • improvement in cognitive scales

Alcohol

  • low moderate consume decrease risk of dementia

Caffeine

  • peak in plasma after 45-120 min, halflife 2.5-4.5 h
  • facilitate learning in passively tasks
  • boost cognitive performance among fatigued individuals

Cardiovascular risk profile

Strongly associated with cognitive decline e dementia
Advantage of being modifiable
risk factor: hypertension, diabetes, dyslipidemia, smoking

vascular desease associated with cerebral hypoperfusion, oxidative stress, neurodegeneration, cognitive decline

AD pure is less than 20%. AD with cardiovascular desease is more common

hypertension e hypercholesterolemia

  • higher level of systolic pressure in midlife = higher risk for dementia
  • also lower level associated with dementia
  • same for coholesterol

diabetes and insulin resistance

  • insuline facilitates cognition
  • deficit in insuline = increased deposition of AB and tau
  • patient with diabetes have lower hippocampal and prefrontal volume

smoking

  • higher exposure to nicotine lower risk of dementia
  • elderly smokers increased risk of dementia

Protective factors

  • physical exercise
  • cognitive engagement
  • social engagement

highly complex mental activity is a protective factor with a dose-dependent effect

Active trial study

cognitive trained subjects have improved cognitive abilities specific to the abilities trained

In MCI is better a multimodal training

It's difficult to isolate depression from dementia:

  • patients with dementia have a higher prevalence of depression
  • depression can be a prodromal sign of dementia
  • depression as a risk factor

Pharmacological strategies

Hormones

  • slow degeneration in women, but reverse after menopause
  • memory problem in menopause
  • estrogenes influence verbal fluency, verbal memory, spatial skills, fine motor skills
  • there are no studies in which estrogen e progesterone are protective against dementia
  • this treatment improve the risk (double risk)

Piracetam

  • protection against cognitive decline in various clinical settins (trauma, cerebrovascular insufficiency, mci)

Acetylcholinesterase inhibitors

  • acetylcholine disfunction is responsible for memory dysfunction in AD e MCI
  • neurodegeneration in AD hit the basak forebrain taht produce acetylcholine
  • block or inhibit the enzime that degrade acetylcholine
  • recommended for AD e vascular dementia

Memantine

  • for moderate e severe dementia with AchE inhibitors

Immune therapy
veccines with antibodies against AB reduce deposition and increase clearance of AB deposition