Neuronal surface autoantibodies in dementia: a systematic review and meta-analysis

Gibson, Lucy; McKeever, Anna; Cullen, Alexis E.; Nicholson, Timothy R; Aarsland, Dag; Zandi, Michael S; Pollak, Thomas A

doi:10.1007/s00415-020-09825-0

Cited by 19 publications

(21 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a recent meta-analysis, we reported that both IgG and IgA/M serum NMDAR antibodies were more prevalent in atypical dementias vs healthy controls, while there was no difference for all-cause dementia. However, the total number of studies was small and “atypicality” was inconsistently defined and in some studies may have been done so post-hoc, necessitating caution in interpretation of this intriguing result 129 .…”

Section: Gaba a R Encephalitismentioning

confidence: 99%

Cognitive impact of neuronal antibodies: encephalitis and beyond

et al. 2020

View full text Add to dashboard Cite

Cognitive dysfunction is a common feature of autoimmune encephalitis. Pathogenic neuronal surface antibodies are thought to mediate distinct profiles of cognitive impairment in both the acute and chronic phases of encephalitis. In this review, we describe the cognitive impairment associated with each antibody-mediated syndrome and, using evidence from imaging and animal studies, examine how the nature of the impairment relates to the underlying neuroimmunological and receptor-based mechanisms. Neuronal surface antibodies, particularly serum NMDA receptor antibodies, are also found outside of encephalitis although the clinical significance of this has yet to be fully determined. We discuss evidence highlighting their prevalence, and association with cognitive outcomes, in a number of common disorders including cancer and schizophrenia. We consider mechanisms, including blood-brain barrier dysfunction, which could determine the impact of these antibodies outside encephalitis and account for much of the clinical heterogeneity observed.

show abstract

Section: Gaba a R Encephalitismentioning

confidence: 99%

Cognitive impact of neuronal antibodies: encephalitis and beyond

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Autoantibody-based clinical neurological and psychiatric syndromes are a rapidly growing field in clinical neuropsychiatry and geriatric psychiatry as they often present with cognitive decline as the first or concomitant symptoms (Gibson et al 2020;Bartels et al 2019;Arino et al 2016;Loane et al 2019;Sechi and Flanagan 2019). A recent study focusing on the increasing frequency of N-methyl-d-aspartate receptor antibodies (NMDAR)-mediated atypical dementia (Gibson et al 2020). In this context, atypical dementia entailing an early-onset and atypical presentation is more often reported to be associated with NMDAR autoantibodies (Gibson et al 2020).…”

Section: Introductionmentioning

confidence: 99%

“…A recent study focusing on the increasing frequency of N-methyl-d-aspartate receptor antibodies (NMDAR)-mediated atypical dementia (Gibson et al 2020). In this context, atypical dementia entailing an early-onset and atypical presentation is more often reported to be associated with NMDAR autoantibodies (Gibson et al 2020). Individual specific autoantibodies such as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit ionotropic glutamate receptor 3 (GluA3) autoantibodies (Palese et al 2020) or contactin-associated protein-like 2 (CASPR2) autoantibodies (Guo et al 2020) have been demonstrated in homogeneous groups of patients with cognitive impairment.…”

Section: Introductionmentioning

confidence: 99%

Neural cell-surface and intracellular autoantibodies in patients with cognitive impairment from a memory clinic cohort

et al. 2021

View full text Add to dashboard Cite

Autoantibody-associated cognitive impairment is an expanding field in geriatric psychiatry. We aim to assess the association between the presence of specific neural autoantibodies and cognitive performance in a memory clinic cohort. 154 patients with cognitive impairment were included between 2019 and 2020 presenting initially in a memory clinic. We evaluated their patient files retrospectively applying epidemiologic parameters, psychopathology, neuropsychology, intracellular and membrane-surface autoantibodies in serum and cerebrospinal fluid (CSF) and markers of neurodegeneration in CSF. In 26 of 154 patients, we searched for neural autoantibodies due to indicators for autoimmunity. In 15/26 (58%) of patients we detected serum and/or CSF autoantibodies. We identified autoantibodies against intracellular or cell-surface antigens in 7 of all 26 (27%) patients with cognitive dysfunction, although we cannot exclude patients with potential specific autoantibodies lacking autoimmune indicators. There were no significant differences between psychopathological and neuropsychological profiles in groups of patients with cognitive impairment comprising patients with autoantibodies (ABS + COG), no autoantibodies (ABS − COG), and Alzheimer’s disease (ADCOG). Concerning our CSF parameters, we detected intrathecal IgG synthesis in 14% of ABS + COG and in 13% of ABS − COG patients, whereas no intrathecal IgG synthesis was found in ADCOG patients. Furthermore, CSF Aß42 was significantly diminished in the ADCOG compared to the ABS + COG group (p < 0.05). In addition, the Aß42/40 ratio was lower in ADCOG patients than in the ABS + COG or ABS − COG group (p < 0.05). Our findings reveal the underestimated occurrence and autoantibodies’ potential role in patients presenting cognitive impairment. Furthermore, the patients with possible Alzheimer’s disease might be differentiated from autoantibody-positive patients via a reduced Aß42 and Aß42/40 ratio in the CSF. The antibody-type varies between patients to a relevant degree, thus demonstrating the need for more research to identify subgroup-specific phenotypes. These pilot study results open an avenue for improving diagnosis and treatment in a memory clinic.

show abstract

“…We thoroughly discuss the potential role of KCNA2 in both cases and provide recommendations for future investigations. We emphasize the importance of taking a systematic diagnostic approach in patients presenting with clinical features signaling an autoimmune-related cognitive decline that they might mimic, but must be differentiated from neurodegenerative diseases, as the therapeutic implications are immense and a delay in inducing effective immunotherapy will compromise the patient’s clinical outcome [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

KCNA2 Autoimmunity in Progressive Cognitive Impairment: Case Series and Literature Review

et al. 2021

View full text Add to dashboard Cite

Autoimmune dementia is a novel and expanding field which subsumes neuropsychiatric disorders with predominant cognitive impairments due to an underlying autoimmune etiology. Progressive dementias with atypical clinical presentation should trigger a thorough diagnostic approach including testing for neural surface and intracellular antibodies to avoid a delay in accurate diagnosis and initiating appropriate therapy. Here, we present two emerging cases of progressive dementia with co-existing serum autoantibodies against the KCNA2 (potassium voltage-gated channel subfamily A member 2) subunit. We found various cognitive deficits with dominant impairments in the memory domain, particularly in delayed recall. One patient presented a subacute onset of then-persisting cognitive deficits, while the other patient’s cognitive impairments progressed more chronically and fluctuated. Cognitive impairments coincided with additional neuropsychiatric symptoms. Both had a potential paraneoplastic background according to their medical history and diagnostic results. We discuss the potential role of KCNA2 autoantibodies in these patients and in general by reviewing the literature. The pathogenetic role of KCNA2 antibodies in cognitive impairment is not well delineated; clinical presentations are heterogeneous, and thus a causal link between antibodies remains questionable. Current evidence indicates an intracellular rather than extracellular epitope. We strongly suggest additional prospective studies to explore KCNA2 antibodies in specifically-defined cohorts of cognitively impaired patients via a systematic assessment of clinical, neuropsychological, neuroimaging, as well as laboratory and CSF (cerebrospinal fluid) parameters, and antibody studies to (1) determine the epitope’s location (intracellular vs. extracellular), (2) the mode of action, and (3) seek co-existing, novel pathogenetic autoantibodies in sera and CSF.

show abstract

Neuronal surface autoantibodies in dementia: a systematic review and meta-analysis

Cited by 19 publications

References 44 publications

Cognitive impact of neuronal antibodies: encephalitis and beyond

Cognitive impact of neuronal antibodies: encephalitis and beyond

Neural cell-surface and intracellular autoantibodies in patients with cognitive impairment from a memory clinic cohort

KCNA2 Autoimmunity in Progressive Cognitive Impairment: Case Series and Literature Review

Contact Info

Product

Resources

About