Thursday, September 15, 2011

Diagnosing Alzheimer's Dementia

Alzheimer's Disease amyloid plaques and neuro-fibrillay tangles in brain tissue
Microscopic picture of the brain showing amyloid plaques and
 neurofibrillary tangles first seen by Alois Alzheimer in 1907

The diagnosis of Alzheimer's disease became headline news when the defence counsel of a prominent citizen of  Pune stated they were awaiting results of his brain MRI to finalise the diagnosis of dementia. Recently a patient's medication was stopped when his neuro-physician declared there were 'no plaques on MRI so it is not a case of Alzheimers'. The caregivers returned to me when his behaviour problems recurred.

Dementia including that of the Alzheimer's type is a clinical diagnosis (Grand 2011). Dementia is characterised by a triad of
  1. Progressive deterioration of mental processes (cognitive abilities)
  2. Behavioural and psychological symptoms of dementia (BPSD)
  3. Difficulties carrying out day-to-day activities (activities of daily living or ADL).  
Alzheimer's Disease is commonest dementia after 65 years of age Alzheimer's dementia has an insidious onset, and progresses gradually and inexorably. This natural course is a key differentiator Alzheimer's from other forms of dementia. Dementia is suspected when a caregiver of an elderly person, or sometimes a person with a family history of dementia, becomes concerned about problems with memory. The diagnosis is purely clinical. No laboratory test or imaging (including MRI) is required to diagnose Alzheimer's disease. These investigations can only help differentiate the other forms of dementia when those are suspected.

Memory problems are a core feature of the disease. These manifest as
  • Difficulty recalling details of recent events (forgets he has already dropped his grandchild to school), personal conversations, or specific elements of a task she is performing (eg, preparing a meal)
  • Asking the same question multiple times while denying repeated questioning
  • Tendency to make up events to fill memory gaps and to give inaccurate responses to questions (what he had for breakfast)
Other common cognitive concerns that could indicate dementia of the Alzheimer or any other type
  • Disoreintation to time and place. As the illness progresses orientation worsens to include problems identifying familiar places, family members, or other well known people.
  • Difficulties with activities of daily living (ADL). Problems with dressing or using common utensils
  • Language impairments resulting in decreased conversational output, word-finding difficulties, and limited vocabulary.
  • Visuo-spatial dysfunction manifest as impaired driving ability, and getting lost
  • Problems with mathematical calculations impair ability to use money and balance finances.
  • Impaired judgement in novel situations (difficulty planning a vacation).
Behavioural and psychological symptoms (BPSD)
  • Depression occurs in up to 50% of individuals with Alzheimer's Dementia, and may be attributed to awareness of cognitive changes
  • Lack of feeling or emotion (apathy) is associated with significant caregiver distress
  • Psychosis generally occurs later in the disease course. Delusions are predominantly paranoid in nature, with fears of personal harm or mistreatment, theft of personal property (usually related to financial matters), and marital infidelity. Hallucinations are less common than delusions, and tend to be visual.
  • Other behavioural symptoms include agitation, wandering, and sleep disturbances.

Diagnosis of Alzheimer's Disease is based on 
  1. Detailed history to identify memory deficits, and other cognitive symptoms and assess their impact on the individual and family.
  2. A thorough clinical exam (mental status examination) confirms the impairments in memory and cognition, and delineates the behavioural and psychiatric symptoms that cause caregivers concern. This usually includes using validated and standardised screening pencil and paper tests. 
  3. Psychological testing confirms and quantifies the impairments across various areas of brain function (memory, language, visuo-spatial), assesses the treatment response, and documents progression of the illness with time.

Laboratory tests including MRI only differentiate Alzheimer's disease from other disorders such as subdural haematoma, brain tumour, hydrocephalus, and dementia associated with vascular disease. Magnetic Resonance Imaging (MRI) has no other clinical utility in Alzheimer's disease. These tests are not required or mandated by any classification system including that of the WHO (ICD) or the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA).

Amyloid plaques, and neurofibrillary tangles are the hallmark of Alzheimer's disease and are required for a definitive diagnosis. These were first discovered by Alois Alzheimer in 1907.  His slides were rediscovered in 1992 and 1997. The rediscovered images show the classical pathological signs of the disease named after him. Amyloid plaques and neurofibrillary tangles are seen on microscopic examination of brain tissue using special staining techniques or by electron microscopy. Therefore the only way to obtain a definitive diagnosis of Alzheimer's disease is to obtain a brain tissue sample by biopsy or on autopsy. No MRI, however advanced can detect plaques.
For the purpose of treatment a probable diagnosis using bedside techniques of history and clinical examination is all that is required to diagnose Alzheimer's disease.

  1. Dickerson BC. Advances in quantitative magnetic resonance imaging-based biomarkers for Alzheimer disease. Alzheimers Res Ther. 2010 Jul 6;2(4):21.
  2. Graeber MB, Kösel S, Egensperger R, Banati RB, Müller U, Bise K, Hoff P, Möller HJ, Fujisawa K, Mehraein P. Rediscovery of the case described by Alois Alzheimer in 1911: historical, histological and molecular genetic analysis. Neurogenetics. 1997 May;1(1):73-80.
  3. Grand JH, Caspar S, Macdonald SW. Clinical features and multidisciplinary approaches to dementia care. J Multidiscip Healthc. 2011;4:125-47. Epub 2011 May 15.
  4. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984 Jul;34(7):939-44.