Young-Onset Dementia

Ridha, Basil H.; Josephs, Keith A.

doi:10.1097/01.nrl.0000186798.86255.69

Cited by 24 publications

(6 citation statements)

References 148 publications

(295 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In any case clinicians should consider treating these TYROBP/DAP12 deficient patients with NAD precursors. Young onset dementia is a distinct phenomenon [256]. Cognitive impairment of the Alzheimer's type is the most common form of dementia and occurs after 65 years of age.…”

Section: Tyrobp/dap12 Adaptor and Associated Trem2 Receptor Repression mentioning

confidence: 99%

Pharmacological Targeting of IDO-Mediated Tolerance for Treating Autoimmune Disease

Penberthy

2007

CDM

View full text Add to dashboard Cite

Cells at the maternal-fetal interface express indoleamine 2,3 dioxygenase (IDO) to consume all local tryptophan for the express purpose of starving adjacent maternal T cells of this most limiting and essential amino acid. This stops local T cell proliferation to ultimately result in the most dramatic example of immune tolerance, acceptance of the fetus. By contrast, inhibition of IDO using 1-methyl-tryptophan causes a sudden catastrophic rejection of the mammalian fetus. Immunomodulatory factors including IFNgamma, TNFalpha, IL-1, and LPS use IDO induction in responsive antigen presenting cells (APCs) also to transmit tolerogenic signals to T cells. Thus it makes sense to consider IDO induction towards tolerance for autoimmune diseases in general. Approaches to cell specific therapeutic IDO induction with NAD precursor supplementation to prevent the collateral non-T cell pathogenesis due to chronic TNFalpha-IDO activated tryptophan depletion in autoimmune diseases are reviewed. Tryptophan is an essential amino acid most immediately because it is the only precursor for the endogenous biosynthesis of nicotinamide adenine dinucleotide (NAD). Both autoimmune disease and the NAD deficiency disease pellagra occur in women at greater than twice the frequency of occurrence in men. The importance of IDO dysregulation manifest as autoimmune pellagric dementia is genetically illustrated for Nasu-Hakola Disease (or PLOSL), which is caused by a mutation in the IDO antagonizing genes TYROBP/DAP12 or TREM2. Loss of function leads to psychotic symptoms rapidly progressing to presenile dementia likely due to unchecked increases in microglial IDO expression, which depletes neurons of tryptophan causing neurodegeneration. Administration of NAD precursors rescued entire mental hospitals of dementia patients literally overnight in the 1930's and NAD precursors should help Nasu-Hakola patients as well. NAD depletion mediated by peroxynitrate PARP1 activation is one of the few established mechanisms of necrosis. Chronic elevation of TNFalpha leading to necrotic events by NAD depletion in autoimmune disease likely occurs via combination of persistent IDO activation and iNOS-peroxynitrate activation of PARP1 both of which deplete NAD. Pharmacological doses of NAD precursors repeatedly provide dramatic therapeutic benefit for rheumatoid arthritis, type 1 diabetes, multiple sclerosis, colitis, other autoimmune diseases, and schizophrenia in either the clinic or animal models. Collectively these observations support the idea that autoimmune disease may in part be considered as localized pellagra manifesting symptoms particular to the inflamed target tissues. Thus pharmacological doses of NAD precursors (nicotinic acid/niacin, nicotinamide/niacinamide, or nicotinamide riboside) should be considered as potentially essential to the therapeutic success of any IDO-inducing regimen for treating autoimmune diseases. Distinct among the NAD precursors, nicotinic acid specifically activates the g-protein coupled receptor (GPCR) GPR109a to produce the...

show abstract

Section: Tyrobp/dap12 Adaptor and Associated Trem2 Receptor Repression mentioning

confidence: 99%

Pharmacological Targeting of IDO-Mediated Tolerance for Treating Autoimmune Disease

Penberthy

2007

CDM

View full text Add to dashboard Cite

show abstract

“…[45] Although investigations of the etiologies and prevalence of early-onset dementia have been performed,[45] in some individuals, the etiology remains indeterminate even after brain biopsy. [4] In young adults (up to 40 years of age), it is very rare to develop dementia without other features of neurological disease, or without features of disease elsewhere in the body. Most cases of progressive cognitive disturbance in this age group are caused by psychiatric illness, alcohol, or other drugs or metabolic disturbance.…”

Section: Discussionmentioning

confidence: 99%

A rare case of gliomatosis cerebri presenting as dementia

et al. 2012

View full text Add to dashboard Cite

Dementia with the onset before the age of 65 years is classified as early-onset dementia. Although uncommon, it has considerable impact on the lives of patients and care givers, alike. A substantial subset of patients may have underlying reversible causes. Yet, many, especially those of the very young may be initially misdiagnosed. A case of young woman with rapid mental decay is described here. She was finally diagnosed with gliomatosis cerebri (GC) involving only right frontal lobe. This atypical radiological feature of GC with primary presentation as memory loss needs special attention and clinicians should be aware of such conditions.

show abstract

“…Some cases shown an insidious progression that is difficult to distinguish from AD, FTD or DLB. The classical presentation is characterized by executive dysfunction, affective dyscontrol (typically emotional incontinence), psychomotor slowing, motor dyscontrol, parkinsonism, imbalance, and a gait impairment (small-step, apraxic or parkinsonian gait) 34,48 .…”

Section: Methodsmentioning

confidence: 99%