G08- Aging and Geriatric CNS Diseases Flashcards Preview

Lecture series G-post midterm neuro > G08- Aging and Geriatric CNS Diseases > Flashcards

Flashcards in G08- Aging and Geriatric CNS Diseases Deck (59):
1

What are homogenous populations?

those where people are equally susceptible to injuries, diseases and death

2

what is mean life expectancy (aka lifespan)

50% are still surviving

3

Take note that the real curve and the ideal survival curve are slightly different

compare the images in lecture of the real vs the ideal

4

Presently life expectancy in the western world is rising due to what?

improvements introduced by the medical profession and rising standards of public health.

5

Over the past 150 years life expectancy has been slowing rising, what are some reasons for the rise over these years

before 1900 --> antiseptics, improved housing
1900-1935 --> hygiene, immunization
1935-1950 --> nutrition, medicine, antibiotics, health education
1950-1960 --> medial progress

6

Healthy life expectancy is the age where seriously debilitating disorders develop, what is the healthy life expectancy?

about 10 years less than life expectancy, meaning that many individuals suffer ill health for the last ten years of their lives

7

In what parts of the world do the highest life expectancies occur?

developed countries of the western world

8

In what parts of the world do lowest life expectancies occur?

in Africa where the HIV/AIDS epidemic has caused a huge fall in expectancy within the last 15 to 20 years

9

Many studies confirm the view that life expectancy is determined by what factor?

socio-economic position (SEP)
combo of education, work status, and income

10

Therefore increased SES correlates to an increased or decreased life span?

Increased SES = longer life span and vice versa

11

The number of ppl in the eldest age group is increasing more than ever due to what??

baby boomers

12

As life expectancy rises so does what, in terms of diseases?

incidence of dementia, expected to triple in the next 25 years

13

Older ppl are more susceptible to age specific impairments. Give some examples of age specific impairments in terms of sensory systems

(i) Visual -->acuity, accommodation and macular degeneration
(ii) Olfactory --> olfactory neuron loss and damage to olfactory epithelium
(iii) Hearing --> loss of inner and outer hair cells and spiral ganglion cells
(iv) Vestibular apparatus --> degenerative changes at several sites
(v) Proprioceptors --> impairment seen particularly in lower limbs

14

Now give some examples of age specific impairments in terms of motor system

(i) Muscle --> loss of mass and replacement with fat deposition
(ii) Gait -- >impairment of gait and postural stability
(iii) Basal Ganglia --> Parkinsons, Huntingtons
(iv) Cerebellum --> ataxia's

15

Finally give some examples of cognitive age specific impairments

(i) Dementia --> Alzeheimers, Pick's Dz
(ii) personality disturbances

16

Brain weight begins to decline past about what age?

about 30

17

What are the morphological changes associated with aging?

fall in neuronal size, dendritic arborization and number of synapses. Gyri become narrower and sulci and fissures enlarge as cells shrink and the ventricles and cisterns enlarge

18

In order what are the top 10 causes of death in high income countries?

(i) Ischemic heart disease
(ii) Stroke
(iii) Trachea
(iv) Alzheimers disease
(v) COPD
(vi) lower respiratory infections
(vii) colon and rectum cancers
(viii) diabetes mellitus
(viiii) hypertensive heart disease
(x) breast cancer

19

what are the top 10 cause of death in low income countries?

(i) ischemic heart disease
(ii) stroke
(iii) lower respiratory infections
(iv) COPD
(V) Diarrheal diseases
(vi) Preterm birth complications
(vii) HIV/AIDS
(viii) Diabetes Mellitus
(viiii) Tuberculosis
(x) cirrhosis of the liver

20

what are some differential diagnoses for dementia?

(i) depression
(ii) communicating hydrocephalus
(iii) subdural hematoma
(iv) dehydration
(v) cerebrovascular disease
(vi) neurological diseases

21

The most common form of Dementia is in what disease?

Alzheimer's Disease
(origin or cause is uncertain)

22

What are the two types of alzheimer's disease?

type-1 : late onset after 65 years
type 2: early onset before 65 years

23

What are the three cardinal signs of Alzheimers Disease?

(i) Neuritic Senile Plaques --> extracellular spherical deposits containing many neuritic and glial processes with amyloid protein core
(ii) Neurofibrillary Tangles --> Intracellular paired helical filaments
(iii) Granulovacuolar Degeneration--> degeneration caused by formation of intracellular circular clear zones of cytoplasm (vacuolation)

24

Degenerating neurons in AD show neurofibrillary tangles associated with senile neuritic plaques in neighboring extracellular space. What regions in the brain show these characteristic lesions?

Hippocampus (CA1)
Neocortex
Amygdala
Basal Forebrain
Locus Ceruleus
Raphe Nuclei
Olfactory Cortex

25

Neuron loss in AD is most notable in what regions?

hippocampus
entorhinal cortex
association cortices
basal nucleus of Meynert Areas of limbic system

26

The CNS in AD shows selective loss of what?

Noradrenergic
dopaminergic
cholinergic neurons

27

what proteins forms the core of the neuritic plaques?

amyloid Beta-Protein

28

Amyloid Beta Protein is derived from what precursor protein?

amyloid precursor protein located in cell membranes

29

What is the function of Amyloid precursor protein (APP)?

the function of APP located in the neuronal cell membrane is not known

30

what chromosome does APP encode for?

21

31

In normal brains the APP is cleaved by alpha-secretase but in the case of AD what is APP cleaved by?

B or gamma-secretase (bad!!)

32

In the brains of patients with AD abnormal cleavage of APP occurs. what does this result in?

release of small peptides into the ECF
cleavage done by Beta-secretase and gamma-secretase causing release of Abeta1-40

33

The molecules of Abeta aggregate to produce what??

fibrillary Abeta deposits forming the central region of senile plaques containing axon terminals, microglia and astrocytes

34

What do TAU proteins contribute to in an AD person?

Neurofibrillary Tangles

35

what are TAU proteins?

TAU proteins form the MAPs that assist in stabilization and axonal transport for microtubules thus found in high concentrations in axons

36

Hyperphosphorylated TAU proteins in degenerating neurons, are the major polypeptide constituents of what in the brains of patients with AD?

Neurofibrillary tangles

37

what are some risk factors for AD?

age
presenilin 1 mutations
presenilin 2 mutations
amyloid precursor protein gene mutations (chromosome 21)
apoE alleles (Chromosome 19) (late onset)
Trisomy 21

38

There are 7 stages in Alzheimers Dementia. Each card will go through a stage of the disease. 1--->

Stage 1: No impairment (normal function)
no memory problems; no symptoms of dementia

39

stage 2 of Alzheimers dementia

Stage 2: Very mild cognitive decline (may be normal age related changes or earliest signs of AD)
memory lapses but NO symptoms of dementia during examination

40

Stage 3 of Alzheimers dementia

Stage 3: Mild cognitive decline (Early-stage alzheimer's can be diagnosed in some, but not all, individuals with these symptoms)
(i) problems coming up with right word or name
(ii) trouble remembering names when introduced to new ppl
(iii) having noticeably greater difficulty performing tasks in social or work settings forgetting material that one has just read
(iv) losing or misplacing a valuable object
(v) increasing trouble with planning or organizing

41

Stage 4 of Alzheimers dementia

Stage 4: Moderate Cognitive Decline (Mild or early-stage Alzheimers Dz)
(i) forgetfulness of recent events
(ii) impaired ability to perform challenging mental arithmetic
(iii) greater difficulty performing complex tasks, such as planning dinner or guests, paying bills or managing finances
(iv) becoming moody or withdrawn, esp in socially or mentally challenging situations

42

Stage 5 of Alzheimers dementia

Stage 5: Moderately severe cognitive decline (moderate or mid stage alzheimer's disease)
(i) be unable to recall their own address or telephone number or the high school or college from which they graduated
(ii) become confused about where they are or what day it is
(iii) have trouble with less challenging mental arithmetic
(iv) need help choosing proper clothing for the season or the occasion
(v) still require no assistance with eating or using the toilet

43

Stage 6 of Alzheimer's Dementia

Stage 6: Severe Cognitive Decline (moderately severe or mid stage Alzheimers Disease )
(i) lose awareness of recent experiences as well as of their surroundings
(ii) remember their own name but have difficulty with their personal history
(iii) Distinguish familiar and unfamiliar faces but have trouble remembering the name of a spouse or caregiver
(iv) need help dressing properly and may, without supervision, make mistakes such as putting pajamas over daytime clothes or shoes on the wrong feet
(v) experience major changes in sleep patterns--> sleeping during the day and becoming restless at night
(vi) need help handling details of toileting
(vii) tend to wander or become lost

44

Stage 7 of Alzheimers Dementia

Stage 7: Very severe cognitive decline (Severe or late stage alzheimer's disease)
(i) lose the ability to respond to their environment, to carry on a conversation and eventually to control movement.
(ii) need help with much of their daily personal care, including eating or using the toilet .
(iii) reflexes are abnormal

45

What are the components of the mini mental test for AD?

(i) orientation
(ii) registration
(iii) naming
(iv) reading

46

One of the treatment options for AD is the use of Donezepil, what does this drug do in order to help AD patients?

increases the concentration of AcH through inhibition of AcHE
for use in the early stages

47

Why are neuroleptics often given to AD patients?

AD patients suffer from psychotic symptoms and need to be treated with D1/D2 receptor blockers
(chlorpromazine or haloperidol)

48

what is the new treatment option for AD patients?

Use of monoclonal Antibodies
Aducanumab --> decreases the amount of amyloid plaques in the brain

49

Parkinson's Disease is another age related disease of the CNS, where does the loss of neurons occur in these patients?

Substantia nigra happens in the 6th and 8th decade

50

In addition to dipigmentation of the substantia nigra what else develops in the brains of Parkinson's patients?

Lewy Bodies develop in associated areas including the substantia nigra, pars compacta, locus ceruleus, basal nucleus of Meynert, raphe nuclei and cerebral cortex
Lewy Bodies are granules made mostly of alpha--synuclein found in presynaptic terminals

51

Huntingtons Disease is another age related disease of the CNS and typically appears in the 5th decade with cognitive and emotional disturbances proceeded by chorea. atrophy of what brain structures are characteristic of HD?

frontal cortex, caudate nucleus and putamen and ASTROGLIOSIS is evident

52

what neurotransmitters show a marked decrease in patients with HD?

GABA and glutamic decarboxylase

53

Amyotropic Lateral Sclerosis appears in the 5th decade as well with retained intellectual capacity. Loss of what neurons occurs in ALS?

loss of anterior horn cells, motor nuclei of brainstem and LMN loss causing initial weakness in hands/limbs
Atrophy of motor neurons, gliosis and extensive loss of myelinated fibers in lateral corticospinal tract

54

Picks disease initially resembles what other age related CNS disease?

AD and may be clinically difficult to distinguish

55

Describe the characteristic findings in Pick's Disease

(i) fatal course within 10 years
(ii) affects women more then men
(iii) usually behavioral disturbances and aphasia
(iv) cortical atrophy usually frontal/temporal and unilateral with marked astrogliosis
(v)Cytoplasmic inclusions known as Pick Bodies (densely packed neurofilaments; distinguishable from AD)

56

Creuzfeld-Jakob Disease also known as Prion Disease has an onset of 4th and 5th decade but incubation of infectious protein (prion, PrP) may be 10-30 years. Describe some other characteristics of Prion Disease

(i) fatal within 2 years
(ii) three origins --> infection, sporadic or familial (mutation of PrP)
(iii) Patients show dementia, motor weakness, ataxia, tremors, rigidity and myoclonus
(iv) neuronal loss, astrogliosis, and cytoplasmic vacuoles in cortex and basal ganglia (giving a spongiform appearance)

57

Trisomy 21 gives rise to down's syndrome, if these patients live past 40 they will develop Alzheimers disease. Why??

amyloid gene that encodes the Abeta precursor

58

There is a new variant of Creuzfeld-Jakob disease that is caused by what?

eating contaminated beef from a cow infected with a related animal prion disease known as bovine spongiform encephalopathy

59

Progeria is rapid aging in children, evident by age 2 and death between 8-21 years of age from heart disease. what is the cause for this disease?

gene mutation causes defective protein that normally holds nucleus and cell together