Neuropathology of Dementia Disorders

Abstract

IntroductionDementia, encompassing deficits in several cognitive domains that are severe enough to interfere with daily functioning [1], in the new DSM V classification is classified within the broad category of major neurocognitive disorders, proposing specific criteria for the various etiologies [2]. Previously defined as the manifestation of deteriorating brain functions over time due to cell deaths in the brain caused by neurodegeneration or any other disease [3], according to recent research dementia is not primarily caused by neuronal cell death/loss, but by dysfunction and loss of synapses [4] in AD [5] and in α-synucleinopathies [6]. Other causes include cholinergic neuronal and axonal abnormalities [7,8], as well as pre-and postsynaptic cortical cholinergic deficits also occurring in early AD [9]. These changes due to disconnection of major nervous circuitries causing default networks [10][11][12][13] have been demonstrated in vivo in early AD [14], suggesting that disease progress is transmitted by neuronal pathways [15]. A prionlike spread of misfolded protein aggregates in the pathogenesis and progression of neurodegeneration is a hot spot of discussion [16][17][18][19][20][21].Both the prevalence and incidence of dementia increase exponentially with age. In 2010, 35.6 million people worldwide lived with dementia, with around 8 million new cases every year. Numbers are expected to double or triple every 5-10 years, to 135 millions in 2050, 16 millions in Europe. In 2010, 58% of all demented people lived in low-cost countries, with their proportion anticipated to rise to 71% in 2050 [22]. According to recent data from China the incidence of dementia was 9.87/1000 person years and the median standardised mortality ratio was 1.94:1 [23]. With the disproportional growth of the elderly population, dementia has become a major public health and socio-economic problem that threatens to become the scourge of our century. The total costs for dementia were US$ 604 billion in 2010 worldwide, up to 70% for social care alone [24], total payments for AD for 2013 were expected to be $ 203 billion in USA alone, not included contributions of unpaid caregivers [25]. Neuropathology of Dementia DisordersKurt A Jellinger* Institute of Clinical Neurobiology, Kenyongasse 18, A 1070, Vienna, Austria AbstractDementia, being not a specific disease but a syndrome characterized by deficits in several cognitive domains, is a major public health and socio-economic problem of our century. It is caused by dysfunction/loss of synapses and neurons inducing default neuronal networks. Despite updated concensus criteria for the clinical diagnosis of the major neurodegenerative disorders and new biomarkers, the diagnostic accuracy ranges from 65 to 96% (for Alzheimer's disease /AD), with a sensitivity versus other dementias of around 85.4% and a specificity of up to 77.7%. Pathologic assessment, using genetic and molecular biological methods, based on homogenous definitions, harmonized interlaboratory and assessment standards, can achiev...

Combination and mutual effect of Alzheimer’s disease and cerebrovascular disease

“…В патогенезе БА ведущее значение придается нарушению метаболизма предшественника амилоидного белка, который вначале располагается диффузно, а затем скапливается в виде так называемых «сенильных» бляшек; морфологическим маркером БА служит также белок тау-протеин, накапливающийся внутри нейронов в форме сплетений фибрилл (нейрофибриллярные сплетения) [2]. Гибель нейронов в коре головного мозга носит диффузный характер с преобладанием в медиобазальных отделах лобных долей, гиппокампе, ассоциативных зонах височной и теменной долей.…”

“…Наиболее частая причина КН, составляющая около 60% всех случаев деменции, -болезнь Альцгеймера (БА), около 10-15% случаев деменции вызваны цереброваскулярным заболеванием (ЦВЗ), сочетание цереброваскулярной патологии и БА отмечается в большинстве случаев деменции [2].…”

Mutation analysis of sporadic early-onset Alzheimer's disease using the NeuroX array

“…Many types of dementia have a neuropathological or clinical crossover, for example, both Parkinson’s disease with dementia (PDD) and Parkinson’s disease without dementia (PD) have alpha-synuclein deposits in the brain and a similar clinical presentation to dementia with Lewy bodies (DLB) (Jellinger, 2014). Mixed dementia has features linked to more than 1 type of dementia, for example AD with cerebrovascular lesions or AD with Lewy bodies (Jellinger, 2014).…”

“…Mixed dementia has features linked to more than 1 type of dementia, for example AD with cerebrovascular lesions or AD with Lewy bodies (Jellinger, 2014). It is not surprising then that some genetic loci identified thus far are associated with multiple types of dementias; the commonest example is that of APOE ε4, which is associated with AD (Corder et al, 1993), posterior cortical atrophy (Carrasquillo et al, 2014) and DLB (Bras et al, 2014).…”

Cerebral Multimorbidity in Aging

“…Although Alzheimer disease (AD) and other neurodegenerative disorders that are caused by deposition of misfolded proteins (proteinopathies) are most prevalent in aged people, about two-thirds of aged human brains contain substantial nonAlzheimer pathology [3][4][5] . Cognitively intact elderlies may show substantial AD-related pathology, while in the oldestold group (age 80+ years) 6,7 , much of cognitive decline may not be due to common neurodegenerative pathologies 8,9 , but to multiple pathologies 10 .…”