3.10.2 Alzheimer’s disease

The Neuropathology of Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is characterized by a gradual decline in cognitive function and memory, along with changes in behaviour, mood, and personality. It is the most common cause of dementia in the elderly and is estimated to affect around 0.9 million people in the United Kingdom alone. AD is a complex and multifactorial disease that involves multiple pathological changes in the brain, including amyloid-beta plaque accumulation, neurofibrillary tangle formation, synaptic loss, and neuroinflammation. Alzheimer’s disease is the most prevalent type of dementia. Despite significant advances in the field, the underlying causes of AD remain unclear and there is no cure for this devastating disease (Alzheimer’s Association, 2021).

Auguste Deter was the first person ever diagnosed with Alzheimer’s disease, presenting with poor memory and comprehension as well as aphasia, disorientation, auditory hallucinations and delusions.

The onset of AD typically occurs in people over the age of 65, although early-onset forms of the disease are also recognized. The symptoms of AD typically progress slowly over time and include memory loss, difficulty in solving problems, confusion, disorientation, and changes in mood and behaviour. In the advanced stages of the disease, individuals may experience severe cognitive and functional impairment, requiring full-time care.

The diagnosis of AD is typically made based on a clinical evaluation, which may include cognitive and neuropsychological testing, medical history and imaging studies. While there is currently no cure for AD, various treatments and therapies are available to help manage the symptoms of the disease, improve quality of life, and delay progression (Sperling, 2011) (Holtzman, 2015).

Diagnosing criteria:

Criteria for diagnosing Alzheimer’s disease:	Summary:
CERAD criterion	The Consortium to Establish a Registry for Alzheimer’s disease (CERAD) criterion evaluates the highest density of neocortical NP from 0 (none) to C (abundant) (Murayama, 2004).
Braak and Braak staging system	The Braak and Braak staging system is based on the topographic distribution of the neurofibrillary lesions NFT and NT. The scale has seven stages (Braak, 1991).
2012 NIA-AA criterion	The 2012 National Institute on Aging and the Alzheimer’s Association (NIA-AA) based criteria on a conceptual model of the pathophysiology in which biomarkers (AB42, tau) and imaging PET/MRI become abnormal (Jack, 2012).

Symptoms:

Alzheimer’s disease does not occur naturally as people age. One of the initial symptoms of Alzheimer’s disease and other dementias is frequent memory loss.

An individual with Alzheimer’s disease symptoms might also have one or more of the following issues in addition to memory issues:

• Memory loss that interferes with daily life, such as asking the same questions
• Repeatedly or frequently getting lost in a familiar setting
• Difficulty managing finances and paying bills.
• A Challenge finishing routine duties at work, at home, or in leisure.
• Reduced or bad judgement.
• Losing things and not being able to go back and find them.
• Mood, attitude, or behaviour changes

(Goedert & Spillantini, 2006).

Management:

The National Institute for Health and Care Excellence (NICE) provides guidelines for the diagnosis and management of AD in the UK. These guidelines recommend that individuals with suspected AD should undergo a comprehensive assessment, including a detailed medical history, physical examination, and cognitive testing. The assessment should also take into account the individual’s functional status, including activities of daily living, and any coexisting medical conditions (NICE, 2019).

Once a diagnosis of AD has been made, the management of the condition typically involves a combination of pharmacological and non-pharmacological interventions. Cholinesterase inhibitors and memantine are the two main classes of drugs that are used to treat AD in the UK. These drugs work by increasing the levels of neurotransmitters in the brain, which can help to improve cognitive function and delay the progression of the disease.

In addition to pharmacological interventions, non-pharmacological interventions, such as cognitive stimulation therapy and activities such as exercise, music therapy, and reminiscence therapy, can be beneficial in managing the symptoms of AD. These interventions can help to improve quality of life and cognitive function and provide individuals with opportunities for socialization and engagement.

References:

(1) Alzheimer’s Association. (2021). Alzheimer’s disease facts and figures. Alzheimer’s & Dementia, 17(3), 365-385.

(2) Braak, H. and Braak, E. (1991). Neuropathological stageing of Alzheimer-related changes. Acta Neuropathologica, 82(4), pp.239–259. doi:10.1007/bf00308809.

(3) Goedert, M., & Spillantini, M. G. (2006). A century of Alzheimer’s disease. science, 314(5800), 777-781.

(4) Holtzman, D. M., & Morris, J. C. (2015). Alzheimer’s disease: the challenge of the second century. Science, 347(6226), 1469-1474.

(5) Jack, C.R., Knopman, D.S., Weigand, S.D., Wiste, H.J., Vemuri, P., Lowe, V., Kantarci, K., Gunter, J.L., Senjem, M.L., Ivnik, R.J., Roberts, R.O., Rocca, W.A., Boeve, B.F. and Petersen, R.C. (2012). An operational approach to National Institute on Aging-Alzheimer’s Association criteria for preclinical Alzheimer disease. Annals of Neurology, [online] 71(6), pp.765–775. doi:10.1002/ana.22628.

(6) Murayama, S. and Saito, Y. (2004). Neuropathological diagnostic criteria for Alzheimer’s disease. Neuropathology, 24(3), pp.254–260. doi:10.1111/j.1440-1789.2004.00571.x.

(7) National Institute for Health and Care Excellence (NICE). (2019). Alzheimer’s Disease and Other Dementias. NICE Pathways.

(8) Sperling, R. A., Aisen, P. S., Beckett, L. A., Bennett, D. A., Craft, S., Fagan, A. M., … & Siemers, E. (2011). Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia, 7(3), 280-292.