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

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 not affected at early stage
• May be due to various etiologies, such as Alzheimer’s disease, cerebrovascular disease, other 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

• 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

• 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 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)