THE EARLY SIGNS OF ALZHEIMER’S

THE EARLY SIGNS OF ALZHEIMER’S

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder of the brain with characteristic progressive decline in cognitive function. It is the most common form of dementia (accounts for 60 to 70% of cases) and substantially increases in aged people (65 years or more). The major features are progressive decline in memory, thinking, language, and learning capacity [1]. Alzheimer’s disease often begins with mild symptoms and later progresses to severe brain damage, which ultimately results in death. The disease was discovered in 1906 by Alois Alzheimer, a German neurologist and psychiatrist [1, 3]. It was first observed in a 51-year-old woman known as Auguste Deter. Her family brought her to Dr. Alzheimer in 1901 after they noticed remarkable changes in her personality and behaviour. The family reported problems with memory, difficulty in speaking and impaired comprehension. Dr. Alzheimer later described Mrs. Deter as having an aggressive form of dementia, manifesting in memory, language and behavioural deficits. He identified many abnormal symptoms such as speech difficulty, agitation, and confusion. He monitored her care all five years, until her death in 1906. After her death, Dr. Alzheimer performed an autopsy. The results showed dramatic shrinkage of her cerebral cortex, fatty deposits in blood vessels, and atrophied brain cells. He discovered neurofibrillary tangles and senile plaques, which have become indicative of AD [1, 3]. The condition was first discussed in medical literature in 1907 and named after Alzheimer in 1910. Diagnosis for AD were earlier limited to individual aged 45 to 65. This eventually broadened to any age after several studies found that the pathological and clinical symptoms almost always occurred together regardless of the person’s age [3]. The first drug for the symptomatic treatment of AD approved by the Food and Drug Administration (FDA) in 1993 was called Cognex® [5] . It targeted memory loss and dementia symptoms. Today, there are a total of 5 drugs approved for the symptomatic treatment of AD [5]. As of June 2012, there were more than 330 clinical trials in progress aimed to better understand, treat, prevent, or cure Alzheimer’s disease [3, 5]. Thirty of these studies have reached the human testing phase and scientists are continually seeking new aspects of the disease to study, as there is still no cure for the disease [4, 5] . The two main forms of AD are Familial and Non-Familial AD.

Familial AD: less than 5% of all AD cases are familial in nature and is often caused by individual genetic mutations transmitted in classic Mendelian fashion. It is often called early-onset familial AD (EOFAD) since the age of onset in these forms of AD is usually early (<65 years) or very early (<50 years) [7] .

Non-Familial AD: Is the non-Mendelian, polygenic or sporadic AD, and it causes about 95% of all AD cases. It is also known as late-onset AD (LOAD) since it has an onset age above 65 years of age [6] .

PRECLINICAL SIGNS OF ALZHEIMER’S

As shown in the diagram above, the preclinical stage of Alzheimer’s is divided into symptomatic and asymptomatic phases. The latter is harder to observe or diagnose because there are no evident symptoms, thus a lot of attention has focused on the symptomatic and mild cognitive impaired (MCI) phase of the disease. Because the most salient features of AD, is memory loss the other subtle features in the preclinical phase is often overlooked by caregivers and healthcare professionals. However, recent research studies have shown that the preclinical stage includes “subtle but identifiable qualitative impairments in verbal and visual memory, visuospatial processing, error control, and subjective neuropsychological complaints” [8]. In the next section I will point out some of the early signs to look out for:

  1. Persistent memory loss
    This includes forgetting recently learned information, inability to recall information, forgetting names or appointments occasionally, forgetting why one came into a room or a planned discussion, etcetera
  2. Struggling to perform familiar tasks
    For instance, losing track of the steps involved in preparing a meal, playing a game, or placing atelephone call. This may manifest as difficulty in planning and completing everyday tasks[2].
  3. Language problems
    Also known as dysphasia [8]. This includes forgetting simple words or substituting with unusual words,thus creating difficulty in speech and writing [2].
  4. Visual-spatial disorientation
    This usually manifest as frequently getting lost in one’s neighbourhood, memory loss of one’s physical location, how they got there and how to get back home. Furthermore, losing track of dates and time may be implicated [2].
  5. Poor or decreased judgement
    This could be for instance, dressing inappropriately (i.e. wearing many clothes on a warm day or fewer clothing on a cold day), making a questionable or debatable decision from time to time (e.g. giving away large sums of money to telemarketers)[2].
  6. Trouble with abstract thinking
    That is, struggling to perform complex mental tasks, such as forgetting what numbers are for and how they should be used [2].
  7. Misplacing objects
    Putting items in unusual places (e.g. putting shoe in the kitchen fridge, car keys in the cupboard, etc.) coupled with difficulty in retracing steps to look for a lost item [2]. Often, this also leads to accusing others of stealing.
  8. Mood and personality changes
    These changes usually include anxiety, depression, paranoia, fear, anger outbursts, rapid mood swings (e.g. from calm to tears to anger for no apparent reasons), impatience, irritability, confusion, and aggression [2].
  9. Loss of initiative
    This includes poor performance at work, sitting in front of the TV for hours, sleeping more than usual and overall loss of motivation [2].
  10. Social withdrawal
    Overall, these symptoms are set to worsen with age or as the disease progresses (see the image above).

RISK FACTORS OF ALZHEIMER’S DISEASE

Recent research studies have also pointed out health risk factors that contribute to the onset and progression of AD. To name a few:

  • Smoking
    Smoking contributes to a variety of subclinical and clinical vascular disorders including atherosclerosis and cerebrovascular disease, which eventually, could lead to increased risk of AD [9]. In addition to the link between smoking and cerebrovascular disease, tobacco smoke also contains many neurotoxins that could contribute to risk of AD through oxidative stress.
  • Physical Inactivity
    Physical inactivity was also reported to potentially contribute to the largest proportion of AD cases in the USA and the third largest worldwide [9]. A potential mechanism by which physical inactivity might contribute to risk of AD and other types of dementia, is its association with increased risk of cardiovascular maladies such as diabetes, hypertension and obesity, which have already associated with increased risk of dementia. Interestingly, physical activity seems to have a direct beneficial effect on brain structure and function [10].
  • Depression
    In the USA, depression has been attributed the second most important comorbidity in AD. Globally, it is the fourth [9]. Although controversy remains regarding whether depression is a true causative risk factor for AD or is a prodromal symptom. Several recent studies with long follow-up periods (10–20 years) have begun to shift the weight of evidence towards the risk factor hypothesis in at least some cases [9].Vascular disease has been suggested as one of the potential mechanisms by which depression could increase risk of dementia and cognitive impairment because there is evidence of a reciprocal relationship between depression and vascular disease, which to the clinical manifestation of AD and dementia [9].
  • Obesity
    Midlife obesity, midlife hypertension, and diabetes potentially contributed to a significant proportion of AD cases worldwide and in the USA [9]. These conditions are inter-related, and probably contribute to AD largely through vascular mechanisms. A collateral effect of obesity is Type 2 diabetes, which has been shown to accelerate memory dysfunction and neuroinflammation in mouse models of AD. In all, evidence suggests that obesity increases the risk for AD by the systematic and chronic presence of inflammatory molecules [11].

WHEN TO SEE A DOCTOR

If you consistently experience any of these symptoms or notice them in a loved one, you should speak to a medical professional. Signs of cognitive decline may signify the onset of dementia or another illness for which doctors can aid. An early diagnosis of Alzheimer’s may help to slow the progression of the disease, ease symptoms and improve quality of life.

REFERENCES

  1. L. Minati, T. Edginton, M.G. Bruzzone, G. Giaccone. Current concepts in Alzheimer’s disease: a multidisciplinary review. Am. J. Alzheimer’s Dis. Other Demen., 24 (2009), pp. 95–121 (Italy).
  2. Bennett P. Leifer, M. (. (2009). Alzheimer’s disease: Seeing the signs early. Journal of the American Academy of Nurse Practitioners.
  3. Béatrice Duthey. Alzheimer Disease and other Dementias (Background Paper 6.11). Priority Medicines for Europe and the World. A Public Health Approach to Innovation” 2013. Available at :http://www.who.int/medicines/areas/priority_medicines/BP6_11Alzheimer.pdf. Last ccessed: 25/04/2015.
  4. Alzheimer’s Association. Alzheimer’s Disease Facts and Figures. Alzheimer’s & Dementia 2015;11(3)332+.
  5. History of Alzheimer’s Disease. Available at: http://www.alzheimers.net/2013-12-30/historyof-alzheimers/ Last accessed: 25/04/2015.
  6. Harald Hampel, Simone Lista, Stefan J. Teipel, Francesco Garaci, Robert Nisticò, Kaj Blennow, Henrik Zetterberg, Lars Bertram, Charles Duyckaerts, Hovagim Bakardjian, Alexander Drzezga, et al. Review: Perspective on future role of biological markers in clinical therapy trials of Alzheimer’s disease: A long-range point of view beyond 2020. Biochemical Pharmacology 88 (2014) 426–449.
  7. B. Dubois, S. Epelbaum, A. Santos, F. Di Stefano, A. Julian, A. Michon, M. Sarazin, H. Hampel. Alzheimer disease: From biomarkers to diagnosis. International meeting of the French society of neurology 2013. Revue neurologique 169 (2013) 744–751.
  8. Nicole S. Schmida, K. I. (2013). Neuropsychological Signs of Alzheimer’s Disease 8 Years Prior to Diagnosis. Journal of Alzheimer’s Disease .
  9. Deborah E. Barnes, Kristine Yaffe. (2011). The Projected Impact of Risk Factor Reduction on Alzheimer’s Disease Prevalence. The Lancet Neurology.
  10. Giselle M.Petzinger, B. F. (2013 ). Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson’s disease. Review .
  11. Prof Michael THenekaMD, Monica JCarsonPhD, Joseph El KhouryMD, Gary E LandrethPhD, FredericBrosseronPhD, Douglas L.Feinstein PhD, Andreas H.Jacobs MD, TonyWyss CorayPhD, Javier Vitorica PhD, Richard M.Ransoh MD et. al (2015). Neuroinflammation in Alzheimer’s disease. Lancet Neurology .
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