Incidental Lewy body disease: Do some cases represent a preclinical stage of dementia with Lewy bodies?

Abstract

Lewy pathology occurs in 8-17% of neurologically-normal people >age 60, termed incidental Lewy body disease, (iLBD). It is often assumed to represent preclinical Parkinson disease (PD). However, some iLBD cases have diffuse pathology inconsistent with preclinical PD. We analyzed iLBD cases (α-synuclein immunohistochemistry) using the Braak PD staging scheme and determined if some had a neuropathological pattern suggestive of preclinical Dementia with Lewy bodies (DLB). Of the 235 brains examined, 34 had iLBD (14.5%) and all but one could be assigned a Braak PD stage. The distribution of α-synuclein pathology in the 33 cases fell into three patterns: (1) Diffuse cortical and subcortical α-synuclein pathology; (2) No cortical asynuclein pathology, but a caudal-to-rostral ascending pattern, primarily involving brainstem; (3) Intermediate between these two categories. Also, 6/33 cases failed to follow the pattern of contiguous spread proposed by Braak. These findings suggest dichotomy in the distribution of iLBD: some cases fit the Braak ascending scheme, conceptually consistent with preclinical PD, whereas others displayed prominent cortical involvement that might represent preclinical DLB. Keywordsincidental Lewy body disease; parkinson disease; dementia with Lewy bodies

Olfactory function and neuropsychological profile to differentiate dementia with Lewy bodies from Alzheimer's disease in patients with mild cognitive impairment: A 5-year follow-up study

“…The olfactory deficits are associated with incidental LB disease [36][37][38] but this symptom is not included in the clinical criteria of the Third Consortium on DLB [12]. While it is uncertain whether incidental LB are a precursor to DLB [39], it is cautiously speculated here that olfactory impairments, as measured by the CCSI, may a preclinical marker of DLB at the MCI stage and aid in the improvement of the diagnostic accuracy of DLB.…”

Parkinson's Disease and Parkinsonism: Neuropathology

“…Some elderly individuals have Lewy bodies confined to the olfactory bulb (Fujishiro et al 2008a;Beach et al 2009) or the amygdala, the latter particularly true if associated with concurrent Alzheimer type pathology (Uchikado et al 2006). Moreover, some neurologically normal individuals have sparse, but widespread Lewy body pathology, even involving the cortex (Parkkinen et al 2005;Frigerio et al 2011), which would seem to violate the theory of progression from brainstem and perhaps fit better with a multicentric disease process from the onset. Clearly, the observed distribution of Lewy bodies is dependent on case selection (Parkkinen et al 2001).…”

Neuropathology of Parkinson’s Disease

“…These studies support the concept that dopamine defi cits begin preclinically, although the loss of dopaminergic nigral neurons is also common in DLB and differentiates LB disorders from AD [ 222 , 223 ]. Initial diffuse Lewy pathology (stages 5 and 6) without clinical PD symptoms could represent a precursor to DLB, suggesting a dichotomy in the distribution of ILBD [ 132 ].…”

“…Single clinicopathological case reports suggested that REM sleep behavior disorder (RBD) may represent ILBD or an early clinical manifestation of PD [ 224 ], and that the lack of symptoms is due to subthreshold pathology [ 225 ]. The time interval between RBD and the onset of Parkinsonian symptoms ranged up to 50 years with a median of 25 years [ 226 ], while others reported that olfaction and color vision identify early-stage α-synmediated neurodegeneration at least 5 years before disease onset [ 227 ].…”