alzheimer's%20disease%20-and-%20dementia
ALZHEIMER'S DISEASE AND DEMENTIA
Dementia is a clinical syndrome characterized by impairment of multiple higher cortical functions that include memory, orientation, thinking, comprehension, calculation, capacity for learning, language, judgment,  executive function and visuo-spatial function. It is usually accompanied or preceded by deterioration in emotional control, social behavior or motivation.
Alzheimer's disease is the most common cause of dementia. Sporadic cases usually present after >60 year while familial types are rare and present in <60 year of age (early-onset dementia).
Short-term memory loss is the most common early symptom. Other spheres of cognitive impairment manifest after several years.

Alzheimer's%20disease%20-and-%20dementia Signs and Symptoms

Definition

Dementia

  • A clinical syndrome characterized by impairment of ≥1 cognitive functions that include memory, orientation, calculation, language, judgment, executive function, visuo-spatial function and visuo-motor speed
  • Usually accompanied or preceded by deterioration in emotional control, social behavior or motivation and sleep disturbances
  • Consciousness is not affected at early stage
  • May occur in Alzheimer’s disease, cerebrovascular disease, neurodegenerative conditions (eg Parkinson's disease dementia, dementia with Lewy bodies) and other diseases affecting the brain
  • Severity and global nature of cognitive impairment and the accompanying functional disability differentiate it from the relatively mild and variable cognitive decline associated with normal aging

Alzheimer’s Disease (AD)

  • Most common cause of dementia
  • Majority are sporadic cases which usually present at ≥65 years of age while familial types are rare and present in <65 years (early-onset dementia)
  • Short-term memory loss is the most common early symptom
  • Other spheres of cognitive impairment manifest after several years
  • After memory loss, loss of executive function, language dysfunction, personality and behavioral changes, increasing difficulty with activities of daily living (ADL) and loss of visuo-spatial function are experienced
  • Neuropsychiatric symptoms (eg depression, irritability, anxiety, apathy, agitation, aggression) are common
  • Seizures and myoclonus may also manifest late in the disease
  • Sleep disturbances (eg insomnia, irregular sleep-wake rhythm disorder, restless leg syndrome, periodic limb movement disorder, rapid eye movement disorder, circadian rhythm disturbances, sleep apnea, nocturnal stridor, excessive daytime sleepiness) are common

Vascular Dementia

  • Reported to be the 2nd most common cause of dementia
  • Dementia caused by the effects of cerebrovascular disease on cognitive functioning
  • May present with an abrupt onset and stepwise progression
  • Suspected in patients with a history of stroke or those with focal neurological signs and symptoms
  • Cognitive deficits will depend on what part of the brain is affected by vascular lesions
  • Prominent impairment of executive functions is the hallmark of the disease
  • May also present subacutely and insidiously with apraxia, progressive decline in gait, attention and planning in the presence of vascular pathology
  • Frequently coexists with Alzheimer’s disease (known as mixed dementia), characterized by a gradual progressive dementia occurring in the setting of known cerebrovascular disease
  • Young-onset vascular dementia may have a genetic origin

Dementia with Lewy Bodies (DLB)

  • Characterized by dementia and parkinsonian features (eg bradykinesia, rigidity and/or postural instability leading to frequent falls), fluctuating cognition, prominent and recurrent visual hallucinations and has more rapid evolution of symptoms than Alzheimer's disease
    • Patients tend to have more problems with executive functions such as planning, prioritizing and sequencing, visuospatial function impairment but perform better with verbal memory
  • Supportive features include neuroleptic sensitivity, repeated falls and syncope or transient loss of consciousness
  • Onset of cognitive symptoms in relation to motor slowing is ≤1 year
  • Important to recognize due to high incidence of life-threatening reactions to antipsychotic medications, particularly the extrapyramidal side effects

Parkinson’s Disease Dementia (PDD)

  • Approximately 3 quarters of older patients with Parkinson’s disease develop dementia after 10 years
  • Characterized by cognitive and motor slowing, memory impairment and executive dysfunction
  • It is difficult to differentiate between DLB and PDD clinically
    • Onset of dementia and parkinsonism in DLB must occur within a year, whereas motoric dysfunction occurs years before dementia (10-15 years) in PDD
  • Timing of onset of cognitive symptoms in relation to motor symptoms is >1 year

Fronto-temporal Dementia (FTD)

  • Also known as frontotemporal lobar degeneration
  • Patients usually present at ages 50-60 and represents a significant proportion of people who present with dementia under the age of 65
  • In early stages, patients present with changes in personality, deterioration of social skills, emotional blunting, early language disturbance, executive dysfunction and significant apathy
    • Patients present with progressive decline in inter-personal skills, loss of emotional responsivity, and with emergence of abnormal behaviors such as disinhibition, obsessions, rituals, stereotypies, and alterations in feeding and other appetitive functions
  • Memory difficulties, apraxia and other features of dementia usually follow later as the disease progresses
  • Brain computed tomography (CT)/magnetic resonance imaging (MRI) will show frontal lobe or anterior temporal atrophy and single-photon emission computed tomography (SPECT) or positron emission tomography (PET) will show frontal hypoperfusion or hypometabolism
  • Course of the disease is progressive and more rapid than Alzheimer's disease

Other Progressive Dementing Disorders

  • Huntington’s disease
    • Autosomal dominant disease affecting the basal ganglia and other subcortical structures
    • Manifests with motor (chorea), mood, behavioral and cognitive symptoms
  • Creutzfeldt-Jakob disease
    • Rapidly progressive encephalopathy
    • Cognitive decline is rapid, usually resulting in death within 1.5 years

Epidemiology

  • An estimated 50 million people globally are living with dementia according to the World Health Organization (WHO) and projected to reach 82 million in 2030
    • Estimated number of people living with dementia in Asia is 22.9 million, in the Americas 9.4 million, in Europe 10.5 million and 4 million in Africa
  • In most countries, the age-standardized prevalence of dementia ranges from 5-7%
    • In people age ≥60 years old, estimated prevalence of dementia ranges from 4.7% in Central Europe to 8.7% in North Africa and the Middle East

Pathophysiology

  • Pathogenesis of Alzheimer’s disease remains unclear but it appears that there is an overproduction and/or decreased clearance of amyloid beta peptides; it also involves hyperphosphorylation of tau (a microtubule-associated protein that aids in microtubule assembly)
  • Extracellular beta-amyloid plaques and intracellular neurofibrillary tangles are the essential neuropathologic changes in Alzheimer’s disease

Etiology

Etiology of Dementia

  • Potentially reversible causes
    • Infections (eg meningitis and encephalitis)
    • Toxic or metabolic encephalopathies (eg hypothyroidism, vitamin B12 deficiency and alcohol-related syndromes)
    • Inflammatory disorders (eg autoimmune encephalopathy)
    • Intracranial neoplasms
    • Hydrocephalus (obstructive or normal-pressure hydrocephalus)
    • Delirium
    • Epilepsy
    • Depression and other psychiatric conditions
    • Drugs that increase anticholinergic burden
    • Traumatic brain injury
    • Sensory impairment (eg hearing or vision loss)
  • Irreversible causes
    • Degenerative diseases (eg Alzheimer’s disease, Parkinson's disease, fronto-temporal dementia, and dementia with Lewy body)
    • Cerebrovascular disease (eg stroke, small-vessel disease)
    • Genetic disorders (eg Down syndrome)
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