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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.

Definition

Dementia

  • A clinical syndrome characterized by impairment of multiple higher cortical 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
  • Consciousness is not affected
  • May occur in Alzheimer’s disease, cerebrovascular disease 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
  • Sporadic cases 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) are common
  • Seizures and myoclonus may also manifest late in the disease

Vascular Dementia

  • Reported to be the 2nd most common cause of dementia
  • Dementia caused by the effects of cerebrovascular disease on cognitive functioning
  • Presents with an abrupt onset and with 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
  • 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)

  • Clinically similar to Alzheimer's disease but usually is characterized by earlier Parkinsonian features (eg bradykinesia, rigidity and/or postural instability leading to frequent falls), fluctuating cognition, prominent and recurrent visual hallucinations and tends to have a more rapid evolution
  • 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
  • Timing of onset of cognitive symptoms in relation to motor symptoms is >1 year
  • *Please see Parkinson’s Disease and Parkinson’s Disease Dementia Management Chart for more details

Fronto-temporal Dementia

  • 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
  • Memory difficulties, apraxia and other features of dementia usually follow later as the disease progresses
  • Course of the disease is usually progressive and tends to be 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, mood, behavioral and cognitive symptoms
  • Creutzfeldt-Jakob disease
    • Rapidly progressive encephalopathy manifesting <40 years of age
    • Cognitive decline is rapid, usually resulting in death within 1.5 years

Epidemiology

  • In 2015, it was found that there was an estimated 47 million people globally that are living with dementia
    • 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

  • Neuritic plaques, extracellular deposits of amyloid beta, and neurofibrillary degeneration are the essential neuropathologic changes in Alzheimer’s disease
  • 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 a microtubule-associated protein that aids in microtubule assembly

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)
    • Neoplasms
    • Hydrocephalus (obstructive or normal-pressure hydrocephalus)
    • Delirium
    • Depression and other psychiatric conditions
    • Drugs that increase anticholinergic burden
    • Sensory impairment (eg hearing or vision loss)
  • Irreversible causes
    • Degenerative diseases (eg Alzheimer’s disease, fronto-temporal dementia and dementia with Lewy body)
    • Cerebrovascular disease (eg vascular dementia)
    • Neurogenetic disorders
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