Cognitive and affective disorders in the elderly

1. Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master's Programmesat the University of Pécs and at the University of Debrecen Identification number: TÁMOP-4.1.2-08/1/A-2009-0011

2. Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master's Programmesat the University of Pécs and at the University of Debrecen Identification number: TÁMOP-4.1.2-08/1/A-2009-0011 Márta Balaskó and Gyula Bakó Molecular and Clinical Basics of Gerontology – Lecture 18 Cognitive and affectivedisordersintheelderly

3. Aging-associated cognitive, affective changes • In healthy aging overall intellectual performance does not 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.

4. 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

5. Dementia: definition and prevalence • Definition • 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.

6. Dementia: prevalence and most frequent forms • Prevalence • 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

7. Senile dementia of the Alzheimer type (SDAT, Alzheimer’s disease) 1 • Definition • 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

8. Prevalence of Alzheimer’s disease 60 50% 50 40 30% 30 Prevalence (%) 16% 20 8% 10 4% 2% 1% 0 60-64 65-69 70-74 75-79 80-84 85+ 95+ Age(years)

9. Senile dementia of the Alzheimer type (SDAT, Alzheimer’s disease)2 • Characteristics • Loss of neurons, synapses and atrophy in the cerebral cortex and certain subcortical regions (temporal and parietal lobes, parts of the frontal cortex) • Pathogenesis • cholinergictheory: reduced synthesis of the acetylcholine • beta-amyloid: dense and insolubledeposits of amyloid beta precursor protein (APP)fragmentsformsenileplaques around neuronsinitiatingdamage • tau protein misfolding: intracellularneurofibrillary tangles causemicrotubules todisintegrate, damaging the neuron’s transport system • Inflammation, oxidativestress, accumulation of aluminiuminbrain, etc.

10. Senile dementia of the Alzheimer type (SDAT, Alzheimer’s disease)3 Phases 1 Mildcognitiveimpairment, preclinicalstagea gradual, hidden, progressiveonsetmaylastfor 7-8 yearssymptoms (memoryloss) aremistakenforstress and aging 2 Earlystageincreasing forgetfulness, difficulties with language, executive functions, agnosia,apraxia, personality changes 3 Moderatestagedependency increasesdifficulty with speech, pathological behavior (agression) andconfusion, delusions 4 Advanced stage completedependency, verbal output decreases, pronouncedmemory decline, patients get bed-ridden, death

11. Senile dementia of the Alzheimer type (SDAT, Alzheimer’s disease) 4 • Prognosis • Average survival is 7 years. Most common causes of death: pressure ulcers, pneumonia • Treatment • 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.

12. Non-Alzheimer dementias (organic brain disorders) • Characteristics • 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.

13. Causes of non-Alzheimer dementias • Intracranial: • Degenerative disorders • Parkinson’s, Pick, Lewy • Huntington • Vascular, post-stroke states • Space occupying lesions • Post-trauma states • polytrauma (boxing, liver) • subdural hematoma, • hemodialysis • Infectious agents • AIDS, prion (Creutzfeldt-Jakob), • neurosyphilis, Lyme disease • meningitis • Extracranial: • Poisons • 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

14. Delirium: definition • Characteristics • 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.

15. Delirium in the elderly: risk factors 1 • Risk factors • 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 withdrawal) • Acute neurological diseases [acute stroke (usually right parietal), meningitis, encephalitis]

16. 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

17. Amnestic syndromes • Definition • 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-KorsakoffSyndromechronic alcoholism, chronic thiamine deficiency • Transient Amnestic Syndromestransient cerebral ischemia, migraine, alcohol intoxication (“blackouts”), drugs (e.g. benzodiazepines, barbiturates, ketamine), head injury (concussion) • Psychogenic amnesiaposttraumatic stress disorder

18. Alcohol abuse and consequencesin the elderly • Prevalence • 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

19. Consequences of alcohol abusein the elderly 1 • Consequences • Alcohol-induced alterations in drug metabolism: • acute competitiveinhibition 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.

20. Consequences of alcohol abusein the elderly 2 • Consequences • 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 alcoholichepatitis, fatty liver or cirrhosis in old individuals. About 50% of elderly patients with cirrhosisdie 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.

21. Depression in the elderly:definition and characteristics • Definition • 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.

22. 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.

23. Factors that make the diagnosis of depression especially difficult • Diagnostic factors: • 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.

24. 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

25. Differential diagnosis of depression (pseudodementia)and dementia PSEUDO-DEMENTIA • keeps complaining • communicates in detail • “I don’t know” • does not want to do DEMENTIA • does not complain • poor communication • replies with mistakes • eager to cooperate