Posterior cortical atrophy
|Posterior cortical atrophy|
|Other names: Biparietal Alzheimer disease|
|Lobes of the human brain|
Posterior cortical atrophy (PCA), also called Benson's syndrome, is a rare form of dementia which is considered a visual variant or an atypical variant of Alzheimer's disease (AD). The disease causes atrophy of the posterior part of the cerebral cortex, resulting in the progressive disruption of complex visual processing. PCA was first described by D. Frank Benson in 1988.
PCA usually affects people at an earlier age than typical cases of Alzheimer's disease, with initial symptoms often experienced in people in their mid-fifties or early sixties. This was the case with writer Terry Pratchett (1948-2015), who went public in 2007 about being diagnosed with PCA. In rare cases, PCA can be caused by dementia with Lewy bodies and Creutzfeldt–Jakob disease.
Symptoms and signs
The main symptom resulting from posterior cortical atrophy is a decrease in visuospatial and visuoperceptual capabilities, since the area of atrophy involves the occipital lobe responsible for visual processing. The atrophy is progressive; early symptoms include difficulty reading, blurred vision, light sensitivity, issues with depth perception, and trouble navigating through space. Additional symptoms include apraxia, a disorder of movement planning, alexia, an impaired ability to read, and visual agnosia, an object recognition disorder. In the two-streams hypothesis damage to the ventral, or “what” stream, of the visual system, located in the temporal lobe, leads to the symptoms related to general vision and object recognition deficits; damage to the dorsal, or “where/how” stream, located in the parietal lobe, leads to PCA symptoms related to impaired movements in response to visual stimuli, such as navigation and apraxia.
As neurodegeneration spreads, more severe symptoms emerge, including the inability to recognize familiar people and objects, trouble navigating familiar places, and sometimes visual hallucinations. In addition, difficulty may be experienced in making guiding movements towards objects, and a decline in literacy skills including reading, writing, and spelling may develop. Furthermore, if neural death spreads into other anterior cortical regions, symptoms similar to Alzheimer's disease, such as memory loss, may result. In PCA where there is significant atrophy in one hemisphere of the brain hemispatial neglect may result – the inability to see stimuli on one half of the visual field. Anxiety and depression are also common symptoms.
Connection to Alzheimer's disease
Studies have shown that PCA may be a variant of Alzheimer's disease (AD), with an emphasis on visual deficits. Although in primarily different, but sometimes overlapping, brain regions, both involve progressive neural degeneration, as shown by the loss of neurons and synapses, and the presence of neurofibrillary tangles and senile plaques in affected brain regions; this eventually leads to dementia in both diseases. In PCA there is more cortical damage and gray matter (cell body) loss in posterior regions, especially in the occipital, parietal, and temporal lobes, whereas in Alzheimer’s there is typically more damage in the prefrontal cortex and hippocampus. PCA tends to impair working memory and anterograde memory, while leaving episodic memory intact, whereas in AD there is typically impaired episodic memory, suggesting some differences still lie in the primary areas of cortical damage.
Over time, however, atrophy in PCA may spread to regions that are commonly damaged in AD, leading to shared AD symptoms such as deficits in memory, language, learning, and cognition. Although PCA has an earlier onset, a diagnosis with Alzheimer’s is often made, suggesting that the degeneration has simply migrated anteriorly to other cortical brain regions.
There is no standard definition of PCA and no established diagnostic criteria, so it is not possible to know how many people have the condition. Some studies have found that about 5 percent of people diagnosed with Alzheimer’s disease have PCA. However, because PCA often goes unrecognized, the true percentage may be as high as 15 percent. Researchers and physicians are working to establish a standard definition and diagnostic criteria for PCA.
PCA may also be correlated with Lewy body disease, Creutzfeldt–Jakob disease, Bálint's syndrome, and Gerstmann syndrome. In addition, PCA may result in part from mutations in the presenilin 1 gene (PSEN1).
The cause of PCA is unknown, and there are no fully accepted diagnostic criteria for the disease. This is partially due to the gradual onset of PCA symptoms, their variety, the rare nature of the disease, and the younger age of onset typically 50–60 years. In 2012, the first international conference on PCA was held in Vancouver, Canada. Continued research and testing will hopefully result in accepted and standardized criteria for diagnosis.
PCA is often initially misdiagnosed as an anxiety disorder or depression. It has been suggested that depression or anxiety may result from the symptoms of decreased visual function, and the progressive nature of the disease. Early visual impairments have often led to a referral to an ophthalmologist, which can result in unnecessary cataract surgery.
Due to the lack of biomarkers for PCA, neuropsychological examinations are advised. Neuroimaging can also assist in the diagnosis of PCA. For PCA and AD neuroimaging is carried out using MRI scans, single-photon emission computed tomography, and positron emission tomography (PET scans). Neuroimages are often compared to those of people with AD to assist diagnosis. Due to the early onset of PCA in comparison to AD, images taken at the early stages of the disease will vary from brain images in AD. At this early stage brain atrophy will be shown to be more centrally located in the right posterior lobe and occipital gyrus, while AD brain images show the majority of atrophy in the medial temporal cortex. This variation within the images will assist in early diagnosis of PCA; however, as the years go on the images will become increasingly similar, due to the majority of PCA also developing to AD later in life because of continued brain atrophy. A key aspect found through brain imaging of PCA patients is a loss of grey matter (collections of neuronal cell bodies) in the posterior and occipital temporal cortices within the right hemisphere.
For some people with PCA, neuroimaging may not give a clear diagnosis; therefore, careful observation in relation to PCA symptoms can also assist in the diagnosis. The variation and lack of organized clinical testing has led to continued difficulties and delays in the diagnosis of PCA.
Specific and accepted treatment for PCA has yet to be discovered; this may be due to the rarity and variations of the disease. At times people with PCA are treated with AD treatments such as, cholinesterase inhibitors, donepezil, rivastigmine, galantamine, and memantine. Antidepressant drugs have also provided some positive effects.
Other treatments such as occupational therapy, or help with adapting to visual changes may help. People with PCA and their caregivers are likely to have different needs than the more typical cases of Alzheimer's disease, and may benefit from specialized support groups, or other groups for young people with dementia. No study to date has been definitive to provide accepted conclusive analysis on treatment options.
- Schott JM, Crutch SJ (February 2019). "Posterior Cortical Atrophy". Continuum (Minneap Minn). 25 (1): 52–75. doi:10.1212/CON.0000000000000696. PMC 6548537. PMID 30707187.
- "Visual variant of Alzheimer's disease - EyeWiki". eyewiki.aao.org. Retrieved 2017-11-07.
- Nestor PJ, Caine D, Fryer TD, Clarke J, Hodges JR (2003). "The topography of metabolic deficits in posterior cortical atrophy (the visual variant of Alzheimer's disease) with FDG-PET". J Neurol Neurosurg Psychiatry. 74 (11): 1521–1529. doi:10.1136/jnnp.74.11.1521. PMC 1738241. PMID 14617709.
- "Posterior Cortical Atrophy". UCSF Memory and Aging Center. University of California, San Francisco. Retrieved 2011-10-22.
- Benson DF, Davis RJ, Snyder BD (July 1988). "Posterior Cortical Atrophy". Archives of Neurology. 45 (7): 789–793. doi:10.1001/archneur.1988.00520310107024. PMID 3390033.
- "Posterior Cortical Atrophy". Martinos Center for Biomedical Imaging. Harvard University. 2009-01-19. Retrieved 2011-10-22.
- "Terry Pratchett pledges $1 million to Alzheimer's research". Alzheimer's Research Trust. 2011-07-29.
- Mendez, Mario; Mehdi Ghajarania; Kent Perryman (14 June 2002). "Posterior cortical atrophy: Clinical characteristics and differences compared to Alzheimer's disease". Dementia and Geriatric Cognitive Disorders. 14 (1): 33–40. doi:10.1159/000058331. PMID 12053130. S2CID 12291848.
- Crutch, Sebastian; Manja Lehmann; Jonathan Schott; Gil Rabinovici; Martin Rosser; Nick Fox (February 2012). "Posterior Cortical Atrophy" (PDF). The Lancet Neurology. 11 (2): 170–178. doi:10.1016/s1474-4422(11)70289-7. PMC 3740271. PMID 22265212.
- Borruat, François-Xavier (18 October 2013). "Posterior Cortical Atrophy: Review of the Recent Literature" (PDF). Neuro-Ophthalmology. 13 (12): 406. doi:10.1007/s11910-013-0406-8. PMID 24136454. S2CID 45579994.
- Goenthals, Maartin; Patrick Santens (20 February 2001). "Posterior cortical atrophy. Two case reports and a review of the literature". Clinical Neurology and Neurosurgery. 103 (2): 115–119. doi:10.1016/s0303-8467(01)00114-7. PMID 11516556. S2CID 46582748.
- Crutch SJ, Schott JM, Rabinovici GD, Boeve BF, Cappa SF, Dickerson BC, Dubois B, Graff-Radford NR, Krolak-Salmon P, Lehmann M, Mendez MF, Pijnenburg Y, Ryan NS, Scheltens P, Shakespeare T, Tang-Wai DF, van der Flier WM, Bain L, Carrillo MC, Fox NC (Jul 2013). "Shining a light on posterior cortical atrophy". Alzheimer's & Dementia. 9 (4): 463–5. doi:10.1016/j.jalz.2012.11.004. PMID 23274153. S2CID 16404876.
- Tsunoda, Ayami; Shuji Iritani; Norio Ozaki (17 March 2011). "Presenile dementia diagnosed as posterior cortical atrophy". Psychogeriatrics. 11 (3): 171–176. doi:10.1111/j.1479-8301.2011.00366.x. PMID 21951958.
- Crutch, Sebastian; Manja Lehmann; Jonathan Schott; Gil Rabinovici; Martin Rosser; Nick Fox (February 2012). "Posterior cortical atrophy". The Lancet Neurology. 11 (2): 170–178. doi:10.1016/s1474-4422(11)70289-7. PMC 3740271. PMID 22265212.
- Kennedy, Jonathan; Manja Lehmann; Magdalena J. Sokolska; Hilary Archer; Elizabeth K. Warrington; Nick C. Fox; Sebastian J. Crutch (25 October 2011). "Visualizing the emergence of posterior cortical atrophy". Neurocase: The Neural Basis of Cognition. 18 (3): 248–257. doi:10.1080/13554794.2011.588180. PMID 22026812. S2CID 20617012.
- Hof, Patrick; Brent Vogt; Constantin Bouras; John Morrison (December 1997). "Atypical Form of Alzheimer's Disease with Prominent Posterior Cortical Atrophy: a Review of Lesion Distribution and Circuit Disconnection in Cortical Visual Pathways". Vision Res. 37 (24): 3609–3625. doi:10.1016/s0042-6989(96)00240-4. PMID 9425534.
- Tsunoda, Ayami; Shuji Iritani; Norio Ozaki (17 March 2011). "Presenile dementia diagnosed as posterior cortical atrophy". Psychogeriatrics. 11 (171–176): 171–176. doi:10.1111/j.1479-8301.2011.00366.x. PMID 21951958.
- "Posterior Cortical Atrophy | Signs, Symptoms, & Diagnosis". Dementia. Retrieved 2016-07-25.
- Nagaratnam, Nages; Kujan Nagaratnam; Daniel Jolley; Allan Ting (6 June 2001). "Dementia following posterior cortical atrophy—a descriptive clinical case report". Archives of Gerontology and Geriatrics. 33 (2): 179–190. doi:10.1016/s0167-4943(01)00179-0. PMID 15374033.
- Crutch, Sebastian J.; Manja Lehmann; Jonathan M. Schott; Gil D. Rabinovici; Martin N. Rossor; Nick C. Fox (February 2012). "Posterior Cortical Atrophy". The Lancet Neurology. 11 (2): 170–178. doi:10.1016/s1474-4422(11)70289-7. PMC 3740271. PMID 22265212.
- Croisile, MD. Bernard; Alexis Brice (September 2004). "Benson's syndrome or Posterior Cortical Atrophy" (PDF). Orphanet Encyclopedia. Retrieved 11 November 2013.
- Goldstein, Martin A.; Iliyan Ivanov; Michael E. Silverman (May 2011). "Posterior Cortical Atrophy: An Exemplar for Renovating Diagnostic Formulation in Neurosychiaty". Comprehensive Psychiatry. 52 (3): 326–333. doi:10.1016/j.comppsych.2010.06.013. PMID 21497228.
- Möller C, van der Flier WM, Versteeg A, Benedictus MR, Wattjes MP, Koedam EL, Scheltens P, Barkhof F, Vrenken H (Feb 2014). "Quantitative Regional Validation of the Visual Rating Scale for Posterior Cortical Atrophy". European Radiology. 24 (2): 397–404. doi:10.1007/s00330-013-3025-5. PMID 24092044. S2CID 14187936.
- Migliaccio R, Agosta F, Toba MN, Samri D, Corlier F, de Souza LC, Chupin M, Sharman M, Gorno-Tempini ML, Dubois B, Filippi M, Bartolomeo P (November 2012). "Brain Networks in Posterior Cortical Atrophy: A Single Case Tractography Study and Literature Review". Cortex. 48 (10): 1298–1309. doi:10.1016/j.cortex.2011.10.002. PMC 4813795. PMID 22099855.
- Caine, Diana (2004). "Posterior Cortical Atrophy: A Review of the Literature". Neurocase. 10 (5): 382–385. doi:10.1080/13554790490892239. PMID 15788276. S2CID 45491962.