Worksheet on Dementia

Worksheet on Dementia

Normal aging

Anatomy and physiology

The process of normal aging in human beings has various effects on their brains. These changes are manifested through various aetiologies demonstrated by changes in vasculature, cells, gross morphology, cognition, and even the molecular structure (Román, 2005). The human brain actually shrinks in size and develops white matter lesions among other changes that affect it from both molecular to morphological ways. Such changes brought about by age affects the brain’s abilities in terms of hormones, memory impairment, and even functioning of the neurotransmitters.

At the most basic considerations, old age in human being brains causes changes as the vasculature deteriorates causing rise in blood pressure and introducing risks. These risks include ischaemia and stroke as the white matter develops lesions (Mori, 2016). Brain activation assumes a more bilateral presentation as the organ attempts to compensate by recruiting more neural networks since the old ones no longer function well. Additionally, the memory functions become compromised as the brain ceases to be able to access certain areas in the normal memory recall process (Boyle & Cahn-Weiner, 2005). Although these changes are influenced by genetics, drug use, and exposure to microbes or radiation, the changes manifested usually include dementia to varying degrees.

Pathology

Aging causes some distinct physical changes in the human brain. Studies reveal that once a person reaches the age of forty their brain looses volume and weight at the rate of five percent each decade. Further research compounds this issue by stating that past the age of seventy, this loss of volume and weight might be on the increase (McKeith, 2016). Most neuroscientists agree that this loss of volume and weight might be attributable to neuronal cell death as the grey matter deteriorates. However, scientists are not entirely sure if the loss of volume is attributable solely to loss of grey matter via neuronal cell death. Indeed, much of the foremost scientific community in this area of expertise agree that neuronal volume rather than the number of neurons is to blame for the loss of grey matter and associated problems (Jellinger, 2013).

Spines, dendritic arbour, and synapse also undergo various changes as the human brain ages. The dendritic arbour grows constantly thus making up for other forms of neural cell death, but this is not enough to counter the loss of cognitive functions as synaptic plasticity losses still occur (Kwon & Choi, 2013). Similarly, white matter loss is a common phenomenon in old age among human beings. Myelin sheath deterioration occurs normally in human brain after the age of forty and has been linked with frontal lobe white matter lesions because of late myelinating. Additionally, the cerebellar vermis, hippocampus, temporal lobe, and cerebellar hemispheres shrink in many occasions as did the prefrontal white matter (Merino & Hachinski, 2005). Interesting, the occipital lobe maintains its volume for longer in a relative context.

Alzheimer’s disease

Prevalence and Incidence in Australia

Statistics by the national health authorities in Australia place the incidence of Alzheimer’s disease (AD) at 50-75 percent of the number of 160,000 dementia sufferers in the country (Quinn, 2013). That means that the number of people suffering from AD in Australia ranges between 80, 000 and 120,000 people. In terms of incidence, the disease affects about 10 percent of all Australians above the age of 65 with more than 20 percent of Australians above the age of 80 suffering from AD among other forms of severe dementia (Quinn, 2013).

Anatomy and Physiology

Alzheimer’s disease (AD) is referred to an irreversible and progressive deterioration of the brain’s cells or neurons leading to loss of primary memory, cognitive functions, reasoning and even judgment. As the disease progresses, the patient may lose all memory and even mental functioning (Benson, 1987). The disease affects both the hippocampus and cerebral cortex causing them to shrink through atrophy. The cerebral cortex is highly complex and important as it controls higher faculties such as reasoning, sensation, thought and motion (Quinn, 2013). Similarly, the hippocampus governs learning processes and information processing processes such as long term memory and recall.

AD causes two main physical evidences that are neuritic plaques and neurofibrillary tangles (Kuller, 1996). The two symptomatic developments are accompanied by the marked reduction of acetylcholine in the cerebral cortex. Because acetylcholine is a crucial chemical precursor for cognitive functioning, a reduction in the catalyst affects cognitive functions adversely (Benson, 1987). It should be noted that neuritic plaques are commonplace among old peoples’ brains. However, patients of AD present with far more of these patches.

Pathology

The development of Alzheimer’s disease (AD) presents with the identification of two distinct markers, namely; intracellular neurofibrillary tangles and extracellular amyloid plaque also called neuritic plagues or patches (Gandy, 1998). Consequently, a pathological investigation follows whereby early onset AD, also referred to as the familial type of AD is caused by mutations in three genes, namely; presenilin 1, presenilin 2, or amyloid precursor protein. This form of AD is more commonly associated with a mixture of genetic and environmental factors manifesting itself anywhere from the age of 65 years.

The second form of Alzheimer’s disease is the more sporadic form which is caused by two risk factors. The first risk factor of sporadic AD is old age whereby the disease just affects an individual once they reach and exceed the age of 65 years (Kuller, 1996). The second cause is the presence of the E4 allele of apolopoprotein E.

Causes and other information

Alzheimer’s disease (AD) is mostly caused by deterioration of parts of the brain, specifically the cerebral cortex and hippocampus. The real cause of this deterioration is still under investigation but genetic, environmental and age-related factors cause the disease (Gandy, 1998). Additionally, the presence of excessive amounts of certain proteins called amyloid plaques also seems to present itself as a causative agent especially in the sporadic forms of the disease. However, the majority of AD is present among patients that had genetic markers and were exposed to certain environmental risks predisposing them to the disease that manifests itself at the age of 60 onwards.

AD reduces the brain’s cognitive functions resulting in problems associated with memory, judgment, reasoning, and motions. While old age affects the brain in a slightly similar manner due to the presence of lesions in the grey matter, AD impacts the brain in a more pronounced, and extremely debilitating manner.

Frontotempolar lobar degeneration (FTLD)

Incidence and prevalence

Based on recent reports, the prevalence of FTLD in Australia is such that between 3000 and 10,000 people suffer from the disease (Jellinger, 2013). Unfortunately, this form of dementia affects relatively younger people compared to other forms of the disease such as AD. FTLD affects people as young as 45 years old and expands its reach up to ages as high as 75 (Miller, 2013). Unfortunately, the youngest Australian on record having been diagnosed with FTLD is 21 years.

Anatomy and Physiology

The brains of people affected by FTLD do not present with amyloid plaques like those of patients suffering from AD. Indeed, this is one distinct anatomical difference differentiating FTLD from other forms of dementia (Miller, 2013). However, the brains of FTLD patients do undergo a level of atrophy that is more severe and accompanies by white matter loss and scarring, also referred to as gliosis.

Almost half the patients suffering from FLTD present with tau, which is neuronal protein that maintains the structure of neurons by binding to the microtubules. Tau also facilitates axonal transport and is included in the process of pathological prognoses (Jellinger, 2013). FTLD mainly affects the frontal, medial, anterior, and inferior temporal lobes of the brain. It also affects the amygdalla as well as the hippocampus making it one of the leading causes of early onset dementia.

Pathology

Early onset dementias may be associated with genetic mutations going on to differentiate in the manner in which FTLD presents itself in pathology or phenotype (Östberg & Bogdanović, 2010). One examples of the pathological difference exists in the form of presentations of muscular weakness, apathy, and withdrawal; all leading to the prognosis of FTD-MND, evidenced by the presence of TDP-43 deposits in the brain (Otsuki, 2012). Others may present with family-specific signs of early onset dementia such as FTLD only to be diagnosed with MAPT-genetic mutations responsible for such dementias (Roeber, Mackenzie, Kretzschmar, & Neumann, 2008). Therefore, the pathologies of individual patients are distinct and individualized.

The neural inclusions or exclusions that characterize the brains of persons suffering from FTD and FTLD have led to the disease being referred to as Pick’s disease after the scientist who discovered the atrophy and related dysfunctions (Roeber, Mackenzie, Kretzschmar, & Neumann, 2008). However, the pathology of FTLD is such that it cannot be done without consideration of the related causes (Otsuki, 2012). Therefore, the FTD-related causes are taupathy-related to MAPT-like mutations that cause Parkinson’s disease, TDP-43 proteinopathy-related due to changes in the brain protein ubiquitin, related to FUS depositions that are TDP-43 negative but ubiquitin positive, and the FTD-UPS related form of dementia that is closest to FTLD.

Causes of FTLD

Like most forms of Frontotemporal Dementia (FTD), Frontotemporal Lobar Degeneration (FTLD) has not distinctly known causes. However, there are genetic markers that just like AD predispose some patients to the condition (Roeber, Mackenzie, Kretzschmar, & Neumann, 2008). Additionally, environmental factors also seem to contribute to the development of the disease especially among its relatively younger demographic.

Vascular Dementia (VaD)

Prevalence and Incidence

In recent studies conducted in Eastern Australia, it was found that up to 28 percent of the every 100, 000 people between the ages of 30 to 64 were suffering from VaD (Boyle & Cahn-Weiner, 2005). Another research endeavor established that up to 12.8 percent of the Australian population between 40 and 65 had VaD (Jellinger, 2005).

Anatomy and Physiology

One mechanism involved in VaD development is ischemic and it occurs due to large vessels disease such as atherosclerosis  (Jellinger, 2005). However, impaired cerebral flow in the absence of infarct as consequence of arterial stenosis has been documented, although its clinical consequences remain to be fully investigated (Boyle & Cahn-Weiner, 2005). Additionally, the alterations of small vessels play a role in causing damage to the cerebral tissue and are potentially responsible for the subsequent development of cognitive alterations.

The most common types of diseases affecting cerebral micro-vessels include arteriosclerosis, lipohyalinosis, cerebral amyloid angiopathy, basal ganglia calcification, CADASIL , other less common intra-cerebral vasculopathies (Kwon & Choi, 2013). Small vessel alterations could also be cuased by incomplete ischemia and selective tissue necrosis (i.e. incomplete infarction) causing a selective neuronal necrosis with sparing of glial cells and microvessels.

Genetic factors play an important role in the aetiology of VaD, in particular, it’s seems to be more important in large-vessel stroke and small vessel stroke than in cryptogenic stroke, and there is no epidemiological evidence for a genetic component in cardioembolic stroke (Merino & Hachinski, 2005).

Pathology

Risk factors involved in cerebrovascular disease are age, sex, some atherogenic disorders or vascular risk factors, genetic factors and inflammation (Merino & Hachinski, 2005). Other potential risk factors like occupational exposure to pesticide, psychological stress or life events, dietary fat intake, family history of stroke, etc.  post-stroke dementia may be the direct consequence of vascular lesions in the brain. Additionally, post-stroke dementia could be the result of pre-existing neuropathological effects AD’s related (Kwon & Choi, 2013). Also, recurrent stroke that is cause by vessel damages and by white matter lesions that may lead to cognitive decline and contribute to post-stroke dementia.

Dementia with Lewy Bodies

Prevalence and Incidence

Dementia with Lewy bodies is the third most frequent cause of dementia in older adults, and accounts for 15–35% of all dementias in Australia (Hasegawa, 2016). Dementia with Lewy bodies is also the most common dementia syndrome associated with Parkinson’s disease with about 52 percent incidence rate (Ikeda, 2016). It is primarily a disease affecting the elderly population. Men may be at higher risk of developing Lewy body dementia than women.

Anatomy and Physiology

The occurrence of Lewy bodies within the cerebral cortex of demented patients was recognized as early as 1961 (Ikeda, 2016). Most of these patients were not initially parkinsonian, but instead presented with dementia (and sometimes psychosis), and developed parkinsonian symptoms only later in their disease, if at all. The distinguishing pathological feature for this group of patients was the appearance of Lewy bodies (or “Lewy type” bodies) in neurons of the cerebral cortex (Hasegawa, 2016). Unlike the classic Lewy bodies of Parkinson’s disease, which are found in pigmented brainstem nuclei, these cortical Lewy bodies are only faintly eosinophilic, are not sharply demarcated by a surrounding halo, and do not show a radial filamentous substructure.

With the new immunohistochemical techniques, significant numbers of cortical Lewy bodies could be found in as many as 15%–25% of demented patients, although many of these patients also showed Alzheimer-type neuropathological changes (Mizuno, 2016). These latter changes, however, were generally restricted to neuritic plaque formation, with a paucity of accompanying neurofibrillary tangles. This combination of neuritic plaques and cortical Lewy bodies, without significant numbers of cortical neurofibrillary tangles, came to be known as the Lewy body variant of Alzheimer’s disease (Economou, Routsis, & Papageorgiou, 2016).

Pathology

Lewy bodies are sought in ten well defined anatomic areas of the brain, using specific immunohistochemical methods. These are then assessed for frequency using a semi-quantitative visual method, rather than actual counting of Lewy bodies (Ikeda, 2016). Based on the distribution and frequency of Lewy bodies, the patient is assigned to one of three stages (or “types”) of Lewy body disease: brainstem-predominant corresponding to classic Parkinson’s disease (McKeith, 2016), limbic or transitional or self-explanatory stage, and diffuse neocortical which corresponds to the earlier reports of diffuse cortical Lewy body disease.

The most specific immunohistochemical method for the detection of Lewy bodies employs antibodies to alpha-synuclein. Anti-ubiquitin antibodies will also detect Lewy bodies, but this technique also highlights Alzheimer-type neurofibrillary changes, and thus is less useful in cases with co-existent Alzheimer pathology (Mizuno, 2016).

References

Benson, D. F. (1987). THE SPECTRUM OF DEMENTIA: A COMPARISON OF THE CLINICAL FEATURES OF AIDS/DEMENTIA AND DEMENTIA OF THE ALZHEIMER TYPE. Alzheimer Disease & Associated Disorders, 1(4), 217-220. doi:10.1097/00002093-198701040-00001

Boyle, P. A., & Cahn-Weiner, D. (2005). Functional Impairment in Vascular Dementia. Vascular Dementia, 171-177. doi:10.1385/1-59259-824-2:171

Economou, A., Routsis, C., & Papageorgiou, S. G. (2016). Episodic Memory in Alzheimer Disease, Frontotemporal Dementia, and Dementia With Lewy Bodies/Parkinson Disease Dementia. Alzheimer Disease & Associated Disorders, 30(1), 47-52. doi:10.1097/wad.0000000000000089

Gandy, S. (1998). Molecular Mechanisms of Dementia. Alzheimer Disease & Associated Disorders, 12(2), 119-120. doi:10.1097/00002093-199806000-00011

Hasegawa, M. (2016). Molecular Biology of Dementia with Lewy Bodies. Dementia with Lewy Bodies, 41-55. doi:10.1007/978-4-431-55948-1_4

Ikeda, M. (2016). Pharmacotherapy in Dementia with Lewy Bodies. Dementia with Lewy Bodies, 215-233. doi:10.1007/978-4-431-55948-1_16

Jellinger, K. A. (2005). The Neuropathologic Substrates of Vascular-Ischemic Dementia. Vascular Dementia, 23-56. doi:10.1385/1-59259-824-2:023

Jellinger, K. A. (2013). Elderly Individuals With FTLD. JAMA Neurology, 70(3), 412. doi:10.1001/2013.jamaneurol.552

Kuller, L. H. (1996). Potential Prevention of Alzheimer Disease and Dementia. Alzheimer Disease & Associated Disorders, 10(Supplement 1), 13-16. doi:10.1097/00002093-199601031-00004

Kwon, J., & Choi, N. (2013). Binswanger-type vascular cognitive impairment no dementia (VCIND) and vascular dementia (VaD). Alzheimer’s & Dementia, 9(4), P788-P789. doi:10.1016/j.jalz.2013.05.1620

McKeith, I. G. (2016). Clinical Diagnostic Criteria for Dementia with Lewy Bodies. Dementia with Lewy Bodies, 59-71. doi:10.1007/978-4-431-55948-1_5

Merino, J. G., & Hachinski, V. (2005). Diagnosis of Vascular Dementia. Vascular Dementia, 57-71. doi:10.1385/1-59259-824-2:057

Miller, B. L. (2013). A Primer of FTLD Neuropathology. Frontotemporal Dementia, 109-130. doi:10.1093/med/9780195380491.003.0007

Mizuno, Y. (2016). Parkinson Symptoms in Dementia with Lewy Bodies. Dementia with Lewy Bodies, 93-109. doi:10.1007/978-4-431-55948-1_8

Mori, E. (2016). Cognitive Impairments of Dementia with Lewy Bodies. Dementia with Lewy Bodies, 73-85. doi:10.1007/978-4-431-55948-1_6

Otsuki, M. (2012). Aphasia and related impairments pertaining to FTLD. Rinsho Shinkeigaku, 52(11), 1224-1227. doi:10.5692/clinicalneurol.52.1224

Quinn, J. (2013). Primary Prevention of Dementia. Dementia, 163-169. doi:10.1002/9781118656082.ch12

Roeber, S., Mackenzie, I. R., Kretzschmar, H. A., & Neumann, M. (2008). TDP-43-negative FTLD-U is a significant new clinico-pathological subtype of FTLD. Acta Neuropathologica, 116(2), 147-157. doi:10.1007/s00401-008-0395-x

Román, G. C. (2005). Clinical Forms of Vascular Dementia. Vascular Dementia, 7-21. doi:10.1385/1-59259-824-2:007

Östberg, P., & Bogdanović, N. (2010). Semantic dementia with lower motor neuron disease showing FTLD-TDP type 3 pathology (sensu Mackenzie). Neuropathology, 31(3), 271-279. doi:10.1111/j.1440-1789.2010.01154.x