Aging & Dementia Flashcards
Life expectancy & aging
- Maximum number of years a human can live has not increased
- Average life expectancy has increased
Aging Theories
- Cellular theories
- DNA Mutation theories
- Inherited factors
- Stress related theories
Do the aging theories occur individually or happen simultaneously?
Aging theories can happen simultaneously
Cellular Theory of Aging
- Maximum lifespan is predetermined (genetically)
- Varies according to species
- Studies of fibroblasts show that if a lifespan of the species is longer, the fibroblasts will divide many more cycles
DNA Mutation Theories of Aging
- Aging occurs as a result of changes in DNA & RNA
- Changes may occur due to mutations caused by external factors, accumulation of errors during transcription, and telomeres
Inheritance & Aging
- Many inherited factors contribute to aging
- Can affect one system but usually affects multiple systems
Oxidative stress & aging
- Free radicals form as oxygen changes to water
- Free radicals accumulate causing mitochondrial damage
- Implicated in Parkinson’s Disease (dopamine breakdown to free radical formation) + Familial ALS (super oxide mutase deficient so O2* builds up)
Aging of the brain - history of study of aging
- Softening of brain
- Vascular dementia (Hardening of arteries)
- Alzheimer’s disease
What # cause of death is Alzheimer’s disease?
7th
What # cause of death is Alzheimer’s disease in >65 years old?
5th
Normal aging of the brain
- Loss of tissue with aging
- Older people - smaller body size and smaller brain size
Ideal Aging
- 1-2% brain volume loss/decade 40-80 years old
- 6-10% total loss by old age (>80 years old)
- Hippocampus loses at faster rate - 5%/decade; total of 25% by 80 years old
- Decrease in cortical thickness
- Ventricular enlargement
How do neurotransmitters change with aging and which ones change?
- Decrease with decrease in number of receptors
- Dopamine, serotonin, GABA
Neuronal Changes with aging occur primarily where?
Basal ganglia & pre frontal cortex
Features of neuronal changes with aging
- Cell body shrinks
- Dendritic tree changes
- Decrease in axon collaterals
- Other mechanisms decline - Ca2+ buffering, enzymes, downregulation of GLU receptors, GABA receptors, LTP, calmodulin, synaptic vesicle
Aging of glial cells
- Less well understood
- Active in myelinization, transport of nutrients, maintaining homeostasis
- More affected in neurotransmission than originally thought
Aging of vasculature
- Small and microvessel disease important contributor to dementia
Postural control & aging
- Decreases because of decline in sensory system, motor system, central processing, dual task abilities
“Aging Machinery” Hypothesis
- Aging is inevitable and irreversible
“Negative Plasticity” Hypothesis
- Aging comes from over-reliance and disuse
- 2 way street - can be partially reversed with training
Healthy Aging
- Exercise
- Control BP
- Healthy diet
- Reduce caloric intake
- Reduce stress
- Stable marriage
- Rest (8 hours sleep)
- Life long learning
Nature v. Nurture
- Aging is inevitable but some people age better than others because of better genes, lifestyles, higher education, higher socioeconomic status, and cognitive reserve
Cognitive reserve concept
- If you start with higher level of intelligence, you have a little more reserve so you can decline in cognitive function a bit before you see a difference in day to day function
Blue Zone Areas
- Areas that live considerably longer than others (consider 7 day adventus)
- Sardinia, Italy
- Okinawa, Japan
- Nicoya, Costa Rica
- Icaria, Greece
- Loma Linda, California
Dementia causes
- 60% Alzheimer’s
- 30-40% vascular
- 15% other (progressive disease, reversible condition, lewy body dementia, alcoholism, endocrine disorder, depression, AIDS, FTD)
Alzheimer’s Disease
- Most common form of dementia due to neuronal degeneration
- Affects all areas of brain especially basal forebrain and cortex
- Some studies show hippocampus and left parietal cortex are affected first
- First sign - memory loss
Characteristics of Alzheimer’s Disease
- Large ventricles
- Cortical atrophy
- Shrunken gyri
- Widen sulci
- Shrunken hippocampus
Alzheimer’s disease - microscopic changes
- Neurofibrillary tangles (NT) - inclusions with neurons, tau proteins
- Amyloid plaques (AP) - in extracellular space
When is definite diagnosis of AD made?
Post mortum
How is probable diagnosis of AD made?
Based on clinical presentation
Neurotransmitter changes with AD
- Decrease in Ach in basal forebrain
- Other systems affected: Noradrenalin, serotonin, dopamine, GABA
Clinical Progression of Alzheimer’s Disease
- Initial onset characterized by short term memory deficits often times noted by family
- Gradual & steady decline in cognitive fxn over a period of years
- Apraxia - later sign
- All systems eventually affected
AD Stage 1
No impairment/normal function
AD Stage 2
Very mild cognitive decline
AD Stage 3
Mild cognitive decline (early-stage Alzheimer’s)
AD Stage 4
Moderate Cognitive Decline (mild or early-stage Alzheimer’s disease)
- Forgetfulness, difficulty performing hard mental arithmetic, complex tasks, personal history, moody/withdrawn
AD Stage 5
Moderately severe cognitive decline (moderate/mid-stage Alzheimer’s)
- Problems with own address/number, confusion about location/day, mental arithmetic that are easier, proper clothing
AD Stage 6
Severe cognitive decline (mod severe/mid-stage Alzheimer’s)
- Lose awareness, difficulty with personal hx, trouble remembering name, dressing confusion, apraxia, changes in sleep, need help with ADLs, personality and behavior changes
Very severe cognitive decline
- Severe/late stage Alzheimer’s
- Lose ability to respond to environment, to carry on conversation, and to control movement
Risk factors of AD: Increased risk with
- Advanced age
- Women
- Previous TBI with unconsciousness
Genetics of AD
- Exposes you to AD but does not predict certainty
- Main one is APP gene which everyone has on chromosome 21 so can relate to Down Syndrome
Treatments of AD
- Acetylcholinesterase inhibitors
Vascular cerebral infarcts
- Other cause of dementia
- 30-40% of dementias
- Seen with AD
- BP and lipid management important
Binswanger’s Disease
- Other cause of dementia
- Affects subcortical white matter
- Disease of microcirculation
- Associated with HTN and other vascular disease
- Seen with shrunken gyri and enlarged ventricles
Symptoms of Lewy Body Dementia
- Pronounced fluctuations in awareness/alertness
- Visual hallucinations
- Parkinson-like motor sign (rigidity, tremor, bradykinesia)
What is average life expectancy after diagnosis of Lewy Body dementia?
8 years
How do you treat Lewy Body Dementia?
Treat cognitive, psychiatric, and motor symptoms of disorder
AIDS related dementia
- High incidence of dementia with AIDS
- Cause unknown
- Can cause other neuro complications of AIDS - infection of CNS, CNS lymphoma, Toxic encephalopathy
