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Common forms of dementia

Dementia is a term used to describe a cluster of symptoms; it is not a disease in and of itself which is a common misconception. The symptoms of dementia may include forgetfulness, memory loss, difficulties orienting oneself, impairments in judgment and problem solving, trouble functioning independently in community affairs, and the need for assistance in personal care. Because dementia describes a group of symptoms, it can manifest itself in different ways. It can occur after an infection, or through a neurodegenerative, vascular, metabolic, or neoplastic process. Dementia is often used as an “umbrella term” to encompass the common symptoms of different types of dementia, and describe them in terms of specific diseases such as Alzheimer’s disease, vascular dementia, and frontotemporal dementia. There is both a need and demand for dementia research because there is no cure, and it is the most prevalent cause of disability amongst Canadians over the age of 65[1]. As well, the aging population has led to an increase in the number of elderly people being institutionalized with dementia, with no available cure or effective treatment. Since there are multiple diseases encompassed by dementia, the focus will be on two common types–frontotemporal dementia and vascular dementia.

1. Alzheimer Society of Canada. Rising Tide: The Impact of Dementia on Canadian Society. (2010) ISBN 978-0-9733522-2-1.

Causes of FTD: C9orf72 Gene Mutation

main article: Causes of FTD: C9orf72 Gene Mutation
author: Maiko Matsuda
Hexanucleotide repeat expansion mutations in the chromosome 9 open reading frame 72 (C9orf72) are commonly found in frontotemporal dementia (FTD) patients, accounting for 25.9% of known FTD cases[1]. This mutation is characterized by duplications of GGGGCC sequences in the gene and is hypothesized to be one of the genetic causes of FTD[1][2]. Although correlations have been identified between FTD patients and C9orf72 mutation carrier, the function of the protein encoded by the C9orf72 gene as well as the mechanism by which the mutation causes FTD remains largely unknown. However, potential roles of the gene and disease mechanisms have been postulated. Further investigation into this gene is expected to provide insight into the disease and play an integral role in finding a cure to FTD.

Figure 1
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The C9orf72 gene. The hexanucleotide repeat region is shown above the arrow.[Bibliography item example4 not found.]
1. van Blitterswijk, M., DeJesus-Hernandez, M., Rademakers, R. (2012). How do C9ORF72 repeat expansions cause amyotrophic lateral sclerosis and frontotemporal dementia: can we learn from other noncoding repeat expansion disorders?. Curr Opin Neurol, 25(6), 689-700
2. DeJesus-Hernandez, M., Mackenzie, I.R., Boeve, B.F., Boxer, A.L., Baker, M., Rutherford, N.J., Nicholson, A.M., Finch, N.A., Flynn, H., Adamson, J., Kouri, N., Wojtas, A., Sengdy, P., Hsiung, G.Y., Karydas, A., Seeley, W.W., Josephs, K.A., Coppola, G., Geschwind, D.H., Wszolek, Z.K., Feldman, H., Knopman, D.S., Petersen, R.C., Miller, B.L., Dickson, D.W., Boylan, K.B., Graff-Radford, N.R., Rademakers, R. (2011). Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron, 72(2), 245-56
3. Zamiri, B., Reddy, K., Macgregor, R.B. Jr, Pearson, C.E. (2014). TMPyP4 Porphyrin Distorts RNA G-quadruplex Structures of the Disease-associated r(GGGGCC)n Repeat of the C9orf72 Gene and Blocks Interaction of RNA-binding Proteins. J Biol Chem, 289(8), 4653-9

MAPT gene and Frontotemporal Dementia

main article: MAPT gene and Frontotemporal Dementia
author: Donya Mohammadi

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Taupathy-Image source:

Frontotemporal dementia (FTD) is the second most common type of dementias. Although causes for most cases are still unknown, approximately 10-15% of the familial cases are genetic based [1]. MAPT is the earliest gene discovered as a possible causal factor for FTD. Over 40 different mutations on this gene can cause toxic aggregation of tau protein that is encoded by MAPT and eventually lead to Frontotemporal dementia. Neuropathology for FTD is heterogeneous meaning that in addition to tau, variety of proteins from 6 other genes can lead to such neurodegeneration [2]. Recent studies, revealed association between haplotypes of MAPT gene and familial Frontotemporal dementia that shines a light in early prediction of this neurodegenerative disease [3]. Additionally, based on improvements in genetics of Frontotemporal Dementia, practical use of genetic counseling for families at risk have captured the attention of neuroscientists in attempting to use this information and help prepare individuals for this disease with late onset [4].

1. Lyer, A., Lapointe, N.E., Zielke, K., Berdynski, M., Guzman, E., Barczak, A., Chodakowaska-Zebrowska, M., Barcikowska, M., Feinstein, S., & Zekanowski, C. (2013). A Novel MAPT Mutation, G55R, in a Frontotemporal Dementia Patient Leads to Altered Tau Function. PLOS One, 8(9).
2. Neumann, M., Tolnay, M., & Mackenzie, I.R. (2009). The molecular Basis of Frontotemporal Dementia. Expert Reviews in Molecular Medicine, 11(23).
3. Canu, E., Boccardi, M., Ghidoni, R., Benussi, L., Testa, C., Pievani, M., Bonetti, M., Binetti, G., & Frisoni, G.B. (2009). H1 Haplotype of the MAPT Gene is Associated With Lower Regional Gray Matter Volume in Healthy Carriers. European Journal of Human Genetics, 17(3), 287-294.
4. Quaid, K.A. (2011). Genetic Counseling for Frontotemporal Dementias. Journal of Molecular Neuroscience, 45(3), 706-709.

Pathology of Vascular Dementia

main article: Pathology of Vascular Dementia
author: Emma Lee

About VaD[5]

Vascular dementia (VaD) is the second most prevalent subset of dementia next to Alzheimer's Disease (AD) as it is found in 5-20% of dementia cases[1]. VaD can result from any condition that damages the vascular system of the brain[2]. The vascular system supplies the brain with blood filled with oxygen and nutrients which are vital to the brain’s function. Damage to the vascular system system results in hypoperfusion (reduced blood flow to the brain). Hypoperfusion may eventually lead to the loss of brain cells, and the onset of VaD[2].

The brain damage which causes VaD cannot be reversed. As a result, most treatments aim to slow or prevent the progression of the disease. Prevention of VaD can be accomplished by treating pre-existing conditions which are able to cause vascular damage. These conditions include hypertension, diabetes, stroke, and heart problems[2]. In particular, hypertension is a major risk factor for VaD independent of its role as a risk factor for stroke[3]. Hypertension can be controlled by way of lifestyle changes and medications; therefore, implementation of these interventions in hypertensive individuals can decrease their risk for VaD. Damage to the vascular system induced by hypertension includes inflammation and oxidative stress in blood vessels[2]. One of the major contributors to oxidative stress in the brain is thought to be nicotinamide adenine dinucleotide phosphate (NADPH) oxidases. NADPH oxidases are a class of enzymes which generate reactive oxygen species (ROS). Since this discovery, NADPH oxidase inhibitors have been examined as potential treatments for the reduction of damage caused by oxidative stress[4].

1. Wiesmann, M., Kiliaan, A. J., Claassen, J. Vascular aspects of cognitive impairment and dementia. J. Cerebr. Blood F. Met. 33, 1696-1706 (2013).
2. Iadecola, C. The Pathobiology of Vascular Dementia. Neuron. 80, 844-866 (2013).
3. Jellinger, K. A. Pathology and pathogenesis of vascular cognitive impairment-a critical update. Front. Aging Neurosci. 5, 1-19 (2013).
4. Drummond, G. R. et al. Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets. Nat. Rev. Drug Discov. 10, 452-471 (2011).

Signs and Symptoms of Frontotemporal Dementia

main article: Signs and Symptoms of Frontotemporal Dementia
author: Mansi Patel

A Patient with Frontotemporal Dementia
A day in the life of an individual suffering from FTD.
Video Source: Youtube, Mayo Clinic

Frontotemporal Dementia (FTD) is a neurodegenerative disorder defined by atrophies in the temporal and frontal cortices [1]. However, atrophies implicated in FTD are not restricted to the frontal and temporal cortices, in recent brain imaging studies it has also been revealed that subcortical and limbic regions as well as more large scale brain networks also degenerate [2][3]. Human functionality is based on networks in the brain that exist through the cooperation and communication of different brain region. The result of atrophies, present in FTD, will alter these essential brain networks resulting in impaired functionality and symptom manifestation [1]. Thus, an understanding of the brain regions involved can elicit greater understanding of the impairments or symptoms that can arise in patients suffering from this form of dementia. These impairments can influence a variety of facets in a patient’s life, such as the social and cognitive domains. Lastly, the knowledge about the symptoms that arise from the degeneration of neuroanatomical structure and networks can further the understanding of the causes for FTD as well as suggest probable treatment options.

1. Woolley, J. D., Gorno-Tempini, M. -., Seeley, W. W., Rankin, K., Lee, S. S., Matthews, B. R., et al. (2007). Binge eating is associated with right orbitofrontal-insular-striatal atrophy in frontotemporal dementia. Neurology,69(14), 1424-1433.
2. Chow, T. W., Izenberg, A., Binns, M. A., Freedman, M., Stuss, D. T., Scott, C. J., et al. (2008). Magnetic Resonance Imaging in Frontotemporal Dementia Shows Subcortical Atrophys. Dementia and geriatric cognitive disorders, 26(1), 79-88.
3. Hodges, J. R., Irish, M., & Piguet, O. (2012). Self-projection and the default network in frontotemporal dementia. Nature Reviews Neurology, 8(3), 152+. doi:

Treatments - Frontotemporal Dementia

main article: Treatments - Frontotemporal Dementia
author: Sonja Stojanovski

A review of current, as well as treatments currently under investigation
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Common therapeutic methods in the treatment of Frontotemporal Dementia include antidepressant medications, such as serotonin reuptake inhibitors (SSRI), and Neuroleptics [1] . Cholinesterase inhibitors initially were shown to improve behaviour symptoms, however over time these drugs worsen the symptoms of FTD [2]. Current treatments seek to address the behavioural side effects that, along with impaired memory and language abilities, are the result of frontotemporal lobar degeneration. These behaviour side effects are varied across the three subtypes of FTD. The first and most common, the behavioural variant of FTD (bvFTD) is accountable for 50% of FTD cases. The symptoms of bvFTD include disinhibition, lack of empathy, apathy and social and emotional changes [1] .The other subgroups are progressive non-fluent aphasia ( PNFA ), and semantic dementia (SD) which are both characterized by gradual deterioration of language. There are currently no FDA-approved medications specifically indicated for the treatment of Frontotemporal Dementia (FTD). Further, there are no treatments that combat the pathology of the disease rather than the symptoms that arise from these pathologies.

1. Perry D, Miller B. (2013). Frontotemporal Dementia. Semin Neurol. 3 (33) 336–341.
2. Mendez MF, Shapira JS, McMurtray A, Licht E. Preliminary findings: behavioral worsening on donepezil in patients with frontotemporal dementia. Am J Geriatr Psychiatry. 15 (1) 84-87.

Vascular Dementia (VaD) and Neuropsychiatric Symptoms (NPS)

main article: Vascular Dementia (VaD) and Neuropsychiatric Symptoms (NPS)
author: Cassandra Anor

Normal Elderly vs. VaD brain
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Axial FLAIR MRI scans of elderly brains

Neuropsychiatric symptoms (NPS) are common in patients with dementia. The most common NPS encountered in dementia are apathy, irritability, agitation, depression, delusions, hallucinations, anxiety, disinhibition, aberrant motor behaviour, sleep disturbances, and eating abnormailities[1]. These symptoms are a major source of patients’ distress, caregiver burden and a primary contributor to institutionalization[2]. Moreover, while psychotropic drugs may alleviate certain NPS, some may have severe adverse effects. Therefore, it is important to better comprehend these symptoms as they have implications for treatment and care. Currently, studies analyzing NPS in vascular dementia (VaD) are becoming more prominent, especially in comparison to the most common dementia type, Alzheimer's disease. Future directions are looking towards not only quantifying these NPS in various dementia types, but are also relating them to specific neuroanatomical correlates, such as white matter hyperintensities and localized regions of atrophy. Because both VaD and AD have specific phenotypes upon MRI analysis, the ultimate goal is to be able to utilize both the classic MRI scans and knowledge of NPS prevalence to better characterize vascular dementia and other dementia types.

1. Cummings, J.L. The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology. 45(5), 579-583 (1997).
2. Huang S., Lee M. Caregiver burden associated with behavioral and psychological symptoms of dementia (BPSD) in Taiwanese elderly. Archives of Gerontology and Geriatrics. 55, 55-59 (2012).

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