Alzheimer’s disease

Notes

## Basic introduction

  • Alzheimer’s disease (AD) is a slowly progressive disease of the brain that is characterized by impairment of memory and eventually by disturbances in reasoning, planning, language, and perception[a]
  • AD is also known as Senile Dementia of the Alzheimer Type (SDAT) or simply Alzheimer’s
  • AD is the most common form of dementia (constituting about 50% of all cases).
  • The global prevalence of AD is likely to increase due to the increased life-expectancy
  • The cause of AD is thought to be the elevated levels of:
  • Beta-amyloid (that form plaques in the spaces between nerve cells)
  • Protein tau (that form tangles inside the nerve cells)
  • The above leads to the degeneration and death of brain cells with steady decline in memory and mental function.

## Genetics of dementia involves the following:

  • Mutations of chromosomes 1, 14 & 21
  • Associated with early-onset familial form of dementia (i.e. dementia < 60yrs)
  • Apo lipoprotein E4 on chromosome 19
  • Associated with late-onset AD

## Statistics

  • About 10% of people aged > 70 years have substantial memory loss and > 50% of them have AD[a]
  • 4% of the global population aged > 65yrs suffer from dementia[e]
  • About 25% of all AD is familial
  • Globally > 15 million people are affected by AD

## Risk factors for AD

  • Family history and genetics
  • Gender (females are more predisposed than males)
  • Mild cognitive impairment
  • History of trauma
  • Other factors such as:
  • Uncontrolled diabetes
  • Hypertension
  • Hypercholesteremia
  • Smoking
Symptoms
  • Dementia
  • It starts with unclear and poorly recognized failure of memory
  • It slowly progresses to a severe and incapacitating conditions

## Stages of development of AD

  • Mild stage with the following symptoms:
  • Language challenges
  • Memory loss
  • Mood swings
  • Personality changes
  • Reduced judgment
  • Moderate stage with the following symptoms:
  • Aggression
  • Agitation
  • Behavioral changes
  • Confusion
  • Impaired long term memory
  • Patient requiring support
  • Personality changes
  • Reduced ability to learn
  • Severe stage with the following symptoms:
  • Affected activities of daily living (ADLs)
  • Gait
  • Incontinence
  • Required long-term care
  • Motor disturbance
Diagnosis
  • Clinical review
  • CT scan
  • MRI
  • Single photon emission computer tomography (SPECT)
  • CSF analysis showing decreased Aβ amyloid 42 and increased protein tau
  • Positron emission tomography (PET)
  • Psychological tests for depression
  • Beta-amyloid plaques and Protein tau tangles are visible microscopically
  • General laboratory tests that may include the following:
  • Full blood count (FBC)
  • Liver function tests (LFTs)
  • Blood chemistry
  • Syphilis
  • TSH
  • Levels of Vitamin B12
Differential
  • Acute confusional state
  • AIDS dementia complex
  • Amnesia
  • Aphasia
  • Chronic CNS infections
  • Chronic drug intoxication
  • Chronic Myelogenous Leukemia
  • CNS angitis
  • Creutzfeld-Jacob disease
  • Delirium
  • Dementia with Lewy bodies
  • Depression
  • Frontotemporal dementia
  • Hypothyroidism
  • Neurosyphilis
  • Normal aging
  • Normal-pressure hydrocephalus
  • Parkinson's disease
  • Prion-Related Diseases
  • Schizophrenia
  • Thyroid disease
  • Vascular dementia
  • Vitamin B12 and thiamine deficiencies
  • Wilson's disease
Prevention
  • None is known
  • Genetic counselling may be useful
Reference
  1. Bird, T. D. (2015). Alzheimer disease overview
  2. Fauci, A. S. (Ed.). (1998). Harrison's principles of internal medicine (Vol. 2, pp. 1888-1889). New York: Mcgraw-hill
  3. Bacanu, S. A., Devlin, B., Chowdari, K. V., DeKosky, S. T., Nimgaonkar, V. L., & Sweet, R. A. (2005). Heritability of psychosis in Alzheimer disease. The American journal of geriatric psychiatry, 13(7), 624-627
  4. Snider, B. J., Fagan, A. M., Roe, C., Shah, A. R., Grant, E. A., Xiong, C., ... & Holtzman, D. M. (2009). Cerebrospinal fluid biomarkers and rate of cognitive decline in very mild dementia of the Alzheimer type. Archives of neurology, 66(5), 638-645.
  5. Hort, J. O. B. J., O’brien, J. T., Gainotti, G., Pirttila, T., Popescu, B. O., Rektorova, I., ... & Scheltens, P. (2010). EFNS guidelines for the diagnosis and management of Alzheimer’s disease. European Journal of Neurology, 17(10), 1236-1248.
Management
  • Cholinesterase inhibitors that are used to delay or slow the symptoms of AD:
  • Donepezil
  • Rivastigmine
  • Galantamine;

(NB: Avoid centrally acting anticholinergic)

  • Partial NMDA receptor antagonists:
  • Memantine (can be used with a cholinesterase inhibitors)
  • Antidepressants and mood stabilizers
  • Sodium valproate (used to treat severe aggression)
  • Citalopram (used to reduce depression and anxiety)
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