Frontotemporal Dementia in Elderly Individuals

Baborie, Atik; Griffiths, Timothy D.; Jaros, Evelyn; Momeni, Parastoo; McKeith, Ian G.; Burn, David J.; Keir, Geoff; Larner, A. J.; Mann, David; Perry, Robert H.

doi:10.1001/archneurol.2011.3323

Cited by 51 publications

(46 citation statements)

References 39 publications

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“…In all 16 expansion carriers, expansion size ranged from ∼5 kb (∼450 repeats) to in excess of 23 kb over 3600 repeats). No pathological variants of GRN , CHMP2B , TARDBP , FUS , MAPT haplotype and APOE alleles were found [18, 19]. …”

Section: Resultsmentioning

confidence: 99%

“…Although, their clinical features were ascertained retrospectively from clinical records, and as such should be treated with some caution, they do seem to show a fairly rapid cognitive decline in common. Two of these patients (patients 2 and 3) can clearly be regarded as late onset FTLD [19]. Patient 1 deteriorated rapidly and died after 10‐month duration of illness, without extensive clinical or neuropsychological follow‐up, although clinical observation led to the impression of FTLD.…”

Section: Discussionmentioning

confidence: 99%

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Accumulation of dipeptide repeat proteins predates that of TDP‐43 in frontotemporal lobar degeneration associated with hexanucleotide repeat expansions in C9ORF72 gene

Baborie

Griffiths

Jaros

et al. 2015

Neuropathology Appl Neurobio

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AimsFrontotemporal lobar degeneration (FTLD) and motor neurone disease are linked by the possession of a hexanucleotide repeat expansion in C9ORF72, and both show neuronal cytoplasmic inclusions within cerebellar and hippocampal neurones which are TDP‐43 negative but immunoreactive for p62 and dipeptide repeat proteins (DPR), these being generated by a non‐ATG RAN translation of the expanded region of the gene.MethodsTwenty‐two cases of FTLD from Newcastle were analysed for an expansion in C9ORF72 by repeat primed PCR and Southern blot. Detailed case note analysis was performed, and blinded retrospective clinical impressions were achieved by review of clinical histories. Sections from all major brain regions were immunostained for TDP‐43, p62 and DPR. The extent of TDP‐43 and DPR pathology in expansion bearers was compared with that in 13 other previously identified cases from the Manchester Brain Bank with established disease.ResultsThree Newcastle patients bearing an expansion in C9ORF72 were identified. These three patients died prematurely, two from bronchopneumonia within 10 months and 3 years of onset, and one from myocardial infarction 3 years after onset. In all three, DPR were plentiful throughout all cerebral cortical regions, hippocampus and cerebellum, but TDP‐43 pathological changes were sparse. The severity of DPR pathological changes in these three patients was similar to that in the Manchester series, although the extent of TDP‐43 pathology was significantly less.ConclusionWidespread accumulation of DPR within nerve cells may occur much earlier than that of TDP‐43 in patients with FTLD bearing expansion in C9ORF72.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Accumulation of dipeptide repeat proteins predates that of TDP‐43 in frontotemporal lobar degeneration associated with hexanucleotide repeat expansions in C9ORF72 gene

Baborie

Griffiths

Jaros

et al. 2015

Neuropathology Appl Neurobio

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“…There is increasing evidence that elderly patients with FTD often present with memory impairment. 5,23,24 In one autopsy study, 64% (n=7) of 11 elderly patients with FTD had anterograde memory loss. 23 Current treatment guidelines do not advise giving ChEIs or memantine treatments to FTD patients.…”

Section: Discussionmentioning

confidence: 99%

Impact of 18FDG PET and 11C-PIB PET brain imaging on the diagnosis of Alzheimer’s disease and other dementias in a regional memory clinic in Hong Kong

Shea

et al. 2016

Hong Kong Med J

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“…FTLD in elderly patients presents features of several phenotypes and morphologic subgroups similar to that seen in the presenile group, though patients with MAPT (tau-gene), but not GRN mutations or FUS pathology are rare or even absent [163]. However, these authors found significantly more frequent hippocampal sclerosis but milder frontal atrophy in the elder group [164], which was confirmed in two cases of FTLD tau aged 85 and 88 years, respectively [165]. Inclusions in FTLD-TDP and ALS but not in FTLD-FUS have properties of amyoid [166].…”

Section: Diagnostic Criteria For Other Dementiasmentioning

confidence: 89%

Neuropathology of Dementia Disorders

Jellinger¹

2014

J Alzheimers Dis Parkinsonism

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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...

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Frontotemporal Dementia in Elderly Individuals

Abstract: To determine whether cases of frontotemporal lobar degeneration (FTLD) do exist in elderly individuals and have clinical and neuropathological features distinct from those with presenile onset.

Cited by 51 publications

References 39 publications

Accumulation of dipeptide repeat proteins predates that of TDP‐43 in frontotemporal lobar degeneration associated with hexanucleotide repeat expansions in C9ORF72 gene

Accumulation of dipeptide repeat proteins predates that of TDP‐43 in frontotemporal lobar degeneration associated with hexanucleotide repeat expansions in C9ORF72 gene

Impact of 18FDG PET and 11C-PIB PET brain imaging on the diagnosis of Alzheimer’s disease and other dementias in a regional memory clinic in Hong Kong

Neuropathology of Dementia Disorders

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