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Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master's Programmes at the University of Pécs and at the University of Debrecen


Academic year: 2022

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Márta Balaskó and Gyula Bakó

Molecular and Clinical Basics of Gerontology – Lecture 18

Medical Biotechnology Master's Programmes

at the University of Pécs and at the University of Debrecen

Identification number: TÁMOP-4.1.2-08/1/A-2009-0011


necessarily deteriorate.

Various cognitive functions decline, while others improve:

• Activity requiring quick reactions and or high degree precision grow weaker.

• Decrease in speed of processing, working memory, inhibitory function and long-term memory are seen.

• Wise consideration based on experience, the ability to

understand and learn from new experience is maintained.


Aging-associated cognitive, affective and psychiatric disorders (outline)

• Dementia

- Neurodegenerative disorders leading to dementia (Alzheimer’s disease)

- Non-Alzheimer dementias (vascular dementia, organic brain disorders)

- Delirium

- Amnestic syndromes

• Alcohol abuse and consequences

• Affective disorders: depression


A serious loss of cognitive ability with maintained vigilance.

Dementia is a clinical diagnosis.

Impairments affect:

• memory (disturbed recognition: agnosia),

• speech (aphasia), language,

• judgement,

• emotional control,

• behavior,

• attention ,

• abstract thinking,

• executive functions (apraxia),

that causes disruption in relationships and social functions.


Dementia: prevalence and most frequent forms


It affects 1% of population at the age of 60, prevalence doubles every year.

It reaches 10 % at 65 years, and 35% above 90 years.

Most prevalent dementias

• Senile dementia of the Alzheimer type (Alzheimer’s disease) 60%

• Non-Alzheimer dementias (organic brain disorders)

• Delirium

• Amnestic syndromes


A (premature) progressive age-associated loss of cognitive

functions (in middle-aged and older) also involving affective and behavioral disturbances.

Risk factors

• age  65 years

• female gender

• low education level (primary school drop-outs: 2× risk)

• positive family anamnesis: 4× risk

• head trauma: 2× risk

• smoking, metabolic syndrome X, atrial fibrillation, stroke, alcohol consumption, genetic predisposition


Prevalence of Alzheimer’s disease

0 10 20 30 40 50 60

60-64 65-69 70-74 75-79 80-84 85+ 95+

Prevalence (%)

Age (years)

1% 2% 4%






Loss of neurons, synapses and atrophy in the cerebral cortex and certain subcortical regions (temporal and parietal lobes, parts of the frontal cortex)


cholinergic theory: reduced synthesis of the acetylcholine beta-amyloid: dense and insoluble deposits of amyloid beta precursor protein (APP) fragments form senile plaques around neurons initiating damage

tau protein misfolding : intracellular neurofibrillary tangles cause microtubules to disintegrate, damaging the neuron’s transport system

Inflammation, oxidative stress, accumulation of aluminium in brain, etc.


Senile dementia of the Alzheimer type (SDAT, Alzheimer’s disease) 3


1 Mild cognitive impairment, preclinical stage

a gradual, hidden, progressive onset may last for 7-8 years symptoms (memory loss) are mistaken for stress and aging 2 Early stage

increasing forgetfulness, difficulties with language, executive functions, agnosia, apraxia, personality changes

3 Moderate stage

dependency increases

difficulty with speech, pathological behavior (agression) and confusion, delusions

4 Advanced stage

complete dependency, verbal output decreases, pronounced memory decline, patients get bed-ridden, death


Average survival is 7 years. Most common causes of death:

pressure ulcers, pneumonia


No drug has been shown to cure the disease or delay progression.

Some drugs alleviate symptoms:

• acetylcholinesterase inhibitors

• glutamate NMDA receptor antagonist

A safe, emotionally supportive environment, physical exercise, optimal diet may improve quality of life of the patient.


Non-Alzheimer dementias (organic brain disorders)


• Symptoms may resemble those of Alzheimer’s disease

• Onset is usually different, changes may occur suddenly or they may not be progressive over time

• In case of metabolic or infectious causes progression may be stopped, even some alleviation of the symptoms is possible.


Degenerative disorders Parkinson’s, Pick, Lewy Huntington

Vascular, post-stroke states Space occupying lesions Post-trauma states

polytrauma (boxing, liver) subdural hematoma,


Infectious agents

AIDS, prion (Creutzfeldt- Jakob),

neurosyphilis, Lyme disease meningitis


alcohol, drugs, medications CO poisoning

Genetic, metabolic causes Wilson’s, hypoglycemias Organ failures

Tumor, metastases failure, renal failure, hydrocephalus heart failure,

thyroid disorders Deficiencies

vitamin B12-, folic acid-, niacin deficiency


Delirium: definition


• It is a clinical syndrome characterized by inattention and acute severe (reversible) cognitive dysfunctions

• In the young, high fever, severe alcohol intoxication, severe metabolic disturbances, etc. may cause delirium

• In the elderly, functional reserve capacity of the brain declines , therefore many milder disorders may lead to delirium

• Delirium affects 14–56% of all hospitalized elderly patients.

Postoperative delirium occurs in 15–53% of surgical

patients over 65 years, and 70–87% among elderly patients admitted to intensive care units.


• Dementia or cognitive impairment

• History of delirium, stroke, neurological disease, falls

• Multiple comorbidities

• Male gender

• Chronic renal or hepatic disease

• Sensory impairment (hearing or vision)

• Immobilization (restraint, catheters)

• Medications (sedative hypnotics, narcotics, anticholinergic, drugs, corticosteroids, polypharmacy, alcohol or drug


• Acute neurological diseases [acute stroke (usually right parietal), meningitis, encephalitis]


Delirium in the elderly: risk factors 2

Risk factors

• Intercurrent illness

(minor infections, iatrogenic complications, anemia, ordinary volume loss, poor nutrition, fracture, trauma)

• Metabolic derangement

severe hypoglycemia, hyper- or hypotonicity

• Surgery

• Alarming environment

(e.g. admission to an intensive care unit)

• Pain

• Emotional distress

• Sustained sleep deprivation


Memory functions are disproportionately impaired compared to other cognitive functions in an otherwise alert patient.

The patient can not remember recent events or learn simple tasks, while performing complex tasks learned previously.

Most common forms

• Wernicke-Korsakoff Syndrome

chronic alcoholism, chronic thiamine deficiency

• Transient Amnestic Syndromes

transient cerebral ischemia, migraine, alcohol intoxication (“blackouts”), drugs (e.g. benzodiazepines, barbiturates, ketamine), head injury (concussion)

• Psychogenic amnesia

posttraumatic stress disorder


Alcohol abuse and consequences in the elderly


Alcohol abuse and alcoholism are prevalent and under-recognized problems in the elderly. About 6 percent of older adults are

considered heavy users of alcohol (13% of men, 2% of women).

The majority of older alcoholic persons (around 66%) grow older with early-onset alcoholism, about 34% develop a problem with alcohol in later life.

Age-related alterations in pharmacokinetics of alcohol

• Gastrointestinal absorption is comparable, distribution is diminished due to decrease in fat free mass.

• Liver perfusion and metabolism in the liver declines slightly.

higher peak serum alcohol


Alcohol-induced alterations in drug metabolism:

• acute competitive inhibition of drug metabolism involving the cytochrome P450 system (microsomal ethanol oxidizing

system=MEOS), e.g. narcotics, tranquillizers leading to suppression of respiratory center

• chronic upregulation of the cytochrome P450 system enhancing clearance of drugs, e.g. coumarins

Falls may be precipitated by alcohol due to acute ataxia, acute hypotension (vasodilatory and diuretic effect), chronic myopathy, cerebellar atrophy and peripheral neuropathy. These falls may lead to hip fractures!

Moderate drinking may exacerbate hypertension, and heavy

drinking increases the risk of stroke. Arrhythmia may develop after an alcohol binge.


Consequences of alcohol abuse in the elderly 2


Ischemic heart disease is responsible for more cardiac deaths among older alcoholics than alcohol-induced cardiomyopathy.

Gastrointestinal bleeding are common among older alcoholics.

The liver is more susceptible for alcoholic hepatitis, fatty liver or cirrhosis in old individuals. About 50% of elderly patients with cirrhosis die within one year of diagnosis.

Elderly patients are more prone to alcohol or its withdrawal-induced delirium .

Chronic alcoholism lead to Wernicke encephalopathy (an acute state of confusion, ataxia and abnormal eye movements) and Korsakoff’s syndrome (an isolated memory deficit manifesting in

confabulation). Global cognitive impairment and alcohol-related dementia based on profound cerebral atrophy is more common in elderly alcoholics.


Depression is a state of low mood and aversion to activity. It may can affect the thoughts, feelings, behavior, and physical well-being of the patient. It usually involves feelings of

sadness, anxiety, emptiness, hopelessness, worthlessness, guilt, irritability or restlessness.

The prevalence of depression among the elderly is increasing.

Their treatment presents a big strain on society.

Depression in the elderly is seldom properly diagnosed. It does not receive proper attention.


Depression in the elderly:

risk factors

It is strongly influenced by such risk factors that become more common with aging:

• genetic factors determine susceptibility for depression

• neurological changes,

• multimorbidity, pain,

• impaired function of sensory organs

• loneliness, isolation

• personal crises, bereavement, anxiety

• reduced adaptability

• lack of perspectives in life, lack of motivation,

• decreased ability to work,

• loss of family background, deficiencies of education, poor social network, negative effects of retirement.


• There is an overlap between the normal phenomena of aging and signs of depression.

• Clinical characteristics may be misleading. Symptoms may be suppressed, non-characteristic or associated with somatization

(complaining about unreal somatic symptoms) and agitation/anxiety.

• It may occur (in a hardly discernible way) in association with chronic diseases and organic cerebral disorders.

Characteristics associated with the patient:

• Losses, bereavement, isolation, shame, refusal of treatment.

• Neither the patient nor the relatives hope for any improvement with the treatment.

Characteristics of health professionals:

• Misconceptions related to old age, lack of empathy and attention.


Depression: prognosis

Poor prognosis, danger signs of suicide:

• advanced age at the onset of depression,

• presence of anxiety in past medical history,

• personality disorders,

• alcohol abuse,

• psychotic signs,

• cognitive impairment,

• organic cerebral disorders, loneliness, poor social circumstances,

• delayed treatment, inadequate management


• keeps complaining

• communicates in detail

• “I don’t know”

• does not want to do

• does not complain

• poor communication

• replies with mistakes

• eager to cooperate



development; Drosophila segmentation Nuclear hormone receptors Glucocorticoid receptor, estrogen receptor,. testosterone receptor, retinoic acid receptors Secondary

• EBF: early B-cell factor, B-cell fate determinant, turns on B- cell specific genes. • Pax5: in its absence cells are blocked at pro-B stage, self renew, broad

ZAP-70 is normally expressed in T cells and natural killer cells and has a critical role in the initiation of T-cell signaling. • ZAP-70 in B cells is used as a prognostic marker

• Cytokines: TNF, IL-1, IL-4, IL-5, IL-6, IL-13, MIP-1a, IL-3,

• After ligand binding, the tyrosine (Y) residue of the ITAM is phosphorylated by tyrosine kinases, and a signaling cascade is generated within the cell.. • An ITAM is present in

Cytokine binding dimerizes the receptor, bringing together the cytoplasmic JAKs, which activate each. other and phosphorylate

Member of a family of proteins termed neutrophins that promote proliferation and survival of neurons; neutrophin receptors are a class of related proteins first identified

• Scavenger receptors bind to bacterial cell wall components such as LPS, peptidoglyan and teichoic acids and stressed, infected, or injured cells. Scavenger