Dementia

• 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
• 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 ≥60 years of age while familial types are rare and present in <60 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

Dementia with Lewy Bodies (DLB)

• Clinically similar to Alzheimer's disease but usually is characterized by earlier Parkinsonian features (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

• 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

• It was hypothesized that dementia is caused primarily by aging and neurodegeneration that is independent of amyloid and vascular disease
• 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 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)

• Irreversible causes
  • Degenerative diseases (eg Alzheimer’s disease, fronto-temporal dementia and dementia with Lewy body)
  • Cerebrovascular disease (eg vascular dementia)
  • Neurogenetic disorders