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.


References
  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.

Sunday, July 31, 2011

Brain effects of cellular phone use

EEG changes with cellular phone radiation
Mobile phone induced EEG changes
Cellular phones affect the brain to cause injury and death through inattention and reaction time delays. Cellular phone radiations also induce abnormal changes in brainwaves. Here we are not concerned with the potential for death due to the cancer generating properties of GSM radiation. We are concerned with the direct and immediate adverse effects of cellular phone conversations.

Cellphones continue to kill their users in Pune. At least two people died crossing the Hadapsar railway tracks while engrossed in conversation. One of them was oblivious to shouting onlookers warning him of the oncoming train. Another cell-bewitched user fell off his eighth-floor balcony while conversing. And of course cellphone use while driving continues to kill despite the ban. All this is besides the cancer risk that the WHO (2011) is unable to disregard.

How distracting is a cellphone conversation?

Any extraneous demand on attention will distract from performance on an ongoing task. If the task itself is critical, as in driving, distractions can be lethal. Even hands-free cellphone conversations while driving cause attention lapses and slow down reaction time (McCartt 2006). These effects are seen in drivers across gender and age groups. The surest way to verify that a crash occurred during mobile phone use is to check billing records. Using this method crashes leading to personal or property damage are found to be four times more common during mobile phone use. When there is a higher mental load in the mobile phone conversation problems with attention and reaction time are magnified (Lin 2006).

The stream of media reported mobile phone related deaths during the performance of everyday tasks highlights the much neglected aspect of non-driving related mobile phone injuries. Pedestrians conversing on a mobile phone cross the road more slowly, are less likely to look for traffic, and take more risks in the face of oncoming traffic (Neider 2010). Pedestrians are less likely to cross a road successfully while using a mobile phone than while listening to music on an iPod. These effects are more pronounced in adolescents.

The risk of injury is related to the need to shift the focus attention from the task on hand to the conversation. Conversing on a mobile phone takes up a significant amount of mental processing ability. Mobile phone conversations increase reaction times and reduce accuracy on task performance. These impairments increase with increasing complexity of the task being interrupted. One can only imagine the effect of a mobile phone interruption on the outcome of an ongoing medical procedure.

Do cellular phone generated electromagnetic waves interfere with brainwaves?

Intriguingly, GSM microwave radiation interacts with and distorts brainwaves. This effect can be directly measured and recorded on an electro-encephalogram (EEG). Electromagnetic fields emitted by cellular phones cause a slowing of brain waves (delta waves) that is not seen in healthy adults during normal wakefulness. These changes persist for up to ten of minutes after the mobile phone is switched off. Children are more vulnerable to these effects as microwave absorption is greatest in an object the size of a child’s head. This radiation also penetrates the thinner skull of an infant with greater ease (Kramarenko 2003).

Brainwaves normally discharge asynchronously when attention is drawn to an event in the environment. This event related de-synchronisation is altered by mobile phone electromagnetic fields. This affects tasks involving memory, especially in children (Krause 2000, 2006). Cellphone radiofrequency waves have a dose dependent effect on tasks attention, concentration and short term memory. Reaction speed decelerates with increasing GSM field intensity. These effects are more pronounced when the responding hand and side of radiation exposure are taken into account (Luria 2009).

These dose dependent radiation effects are also seen when cellular phone use also alters brainwave patterns (spindle activity) during slow-wave sleep. These effects are long lasting, and indicate a non-thermal effect. The thalamus, a part of the brain that processes sensation, is responsible for generating sleep spindle activity and may be especially susceptible to cellphone radiation (Regel 2007).

Walk and talk is a bad idea

References
  1. Robert Baan, Yann Grosse, Béatrice Lauby-Secretan, Fatiha El Ghissassi, Véronique Bouvard, Lamia Benbrahim-Tallaa, Neela Guha, Farhad Islami, Laurent Galichet, Kurt Straif, on behalf of the WHO International Agency for Research on Cancer Monograph Working Group. Carcinogenicity of radiofrequency electromagnetic fields. The Lancet Oncology, Volume 12, Issue 7, Pages 624 - 626, July 2011 doi:10.1016/S1470-2045(11)70147-4
  2. Kemker BE, Stierwalt JA, LaPointe LL, Heald GR. Effects of a cell phone conversation on cognitive processing performances. J Am Acad Audiol. 2009 Oct;20(9):582-8.
  3. Kramarenko AV, Tan U. Effects of high-frequency electromagnetic fields on human EEG: A brain mapping study. Intern. J. Neuroscience, 113:1007–1019, 2003 DOI: 10.1080/00207450390220330
  4. Krause CM, Sillanmäki L, Koivisto M, Häggqvist A, Saarela C, Revonsuo A, Laine M, Hämäläinen H.  Effects of electromagnetic fields emitted by cellular phones on the electroencephalogram during a visual working memory task. Int J Radiat Biol. 2000 Dec;76(12):1659-67.
  5. Krause CM, Björnberg CH, Pesonen M, Hulten A, Liesivuori T, Koivisto M, Revonsuo A, Laine M, Hämäläinen H. Mobile phone effects on children's event-related oscillatory EEG during an auditory memory task. Int J Radiat Biol. 2006 Jun;82(6):443-50.
  6. Lin CJ, Chen HJ. Verbal and cognitive distractors in driving performance while using hands-free phones. Percept Mot Skills. 2006 Dec;103(3):803-10.
  7. Luria R, Eliyahu I, Hareuveny R, Margaliot M, Meiran N. Cognitive effects of radiation emitted by cellular phones: the influence of exposure side and time. Bioelectromagnetics. 2009 Apr;30(3):198-204.
  8. McCartt AT, Hellinga LA, Bratiman KA. Cell phones and driving: review of research. Traffic Inj Prev. 2006 Jun;7(2):89-106.
  9. Mark B. Neider, Jason S. McCarley, James A. Crowell, Henry Kaczmarski, Arthur F. Kramer. Pedestrians, vehicles, and cell phones. Accident Analysis and Prevention 42 (2010) 589–594
  10. Regel SJ, Tinguely G, Schuderer J, Adam M, Kuster N, Landolt HP, Achermann P. Pulsed radio-frequency electromagnetic fields: dose-dependent effects on sleep, the sleep EEG and cognitive performance. J Sleep Res. 2007 Sep;16(3):253-8.