Neuropathological subtypes of Alzheimer’s disease

ArticleinActa Neuropathologica 123(1):153-4 · January 2012with3 Reads
DOI: 10.1007/s00401-011-0889-9 · Source: PubMed
    • "Likewise, Group B had their first GL event earlier than Group A in the clinical course of AD which indicates that GL was among the incipient symptoms for Group B but not for Group A. Whether these differences resulted from the progression of AD, PwAD's premorbid ability, or the effect of the subtype variation of clinical AD [35, 36] is unknown. Previous studies proposed the existence of subtypes under the diagnosis of AD according to the heterogeneity of neuropathology or clinical manifestation [35, 37, 38]. Although the number of subtypes may differ from one study to another because of methodological issues, the primary classifications are typical and atypical AD; the former is characterized by anterograde episodic memory impairment and the latter may include other cognitive deficits such as impairment in abstract reasoning, and verbal fluency [39] . "
    [Show abstract] [Hide abstract] ABSTRACT: Getting lost (GL) is a serious problem for people living with Alzheimer’s disease (PwAD), causing psychological distress in both PwAD and caregivers, and increasing the odds of being institutionalized. It is thus important to identify risk factors for the GL events in PwAD. Between April 2009 and March 2012, we invited 185 community-dwelling PwAD and their caregivers to participate in this study. At the baseline, 95 had experienced GL (Group B); the remaining 90 (Group A) had not. We focused on the incidence of GL events and the associated factors by way of demographic data, cognitive function assessed by the Cognitive Ability Screening Instrument (CASI), and spatial navigation abilities as assessed by the Questionnaire of Everyday Navigational Ability (QuENA). After a 2.5-year period, the incidence of GL in Group A was 33.3% and the recurrence of GL in Group B was 40%. Multiple logistic regression analysis revealed that the inattention item on the QuENA and orientation item on the CASI had independent effects on the GL incidence, while the absence of a safety range was associated with the risk of GL recurrence. During the 2.5 years, the PwAD with GL incidence deteriorated more in the mental manipulation item on the CASI than those without. We suggest that before the occurrence of GL, the caregivers of PwAD should refer to the results of cognitive assessment and navigation ability evaluation to enhance the orientation and attention of the PwAD. Once GL occurs, the caregivers must set a safety range to prevent GL recurrence, especially for younger people.
    Full-text · Article · May 2016
    • "Likewise, Group B had their first GL event earlier than Group A in the clinical course of AD which indicates that GL was among the incipient symptoms for Group B but not for Group A. Whether these differences resulted from the progression of AD, PwAD's premorbid ability, or the effect of the subtype variation of clinical AD [35, 36] is unknown. Previous studies proposed the existence of subtypes under the diagnosis of AD according to the heterogeneity of neuropathology or clinical manifestation [35, 37, 38]. Although the number of subtypes may differ from one study to another because of methodological issues, the primary classifications are typical and atypical AD; the former is characterized by anterograde episodic memory impairment and the latter may include other cognitive deficits such as impairment in abstract reasoning, and verbal fluency [39] . "
    [Show abstract] [Hide abstract] ABSTRACT: Getting lost (GL) is a serious problem for people living with Alzheimer's disease (PwAD), causing psychological distress in both PwAD and caregivers, and increasing the odds of being institutionalized. It is thus important to identify risk factors for the GL events in PwAD. Between April 2009 and March 2012, we invited 185 community-dwelling PwAD and their caregivers to participate in this study. At the baseline, 95 had experienced GL (Group B); the remaining 90 (Group A) had not. We focused on the incidence of GL events and the associated factors by way of demographic data, cognitive function assessed by the Cogni-tive Ability Screening Instrument (CASI), and spatial navigation abilities as assessed by the Questionnaire of Everyday Navigational Ability (QuENA). After a 2.5-year period, the incidence of GL in Group A was 33.3% and the recurrence of GL in Group B was 40%. Multiple logistic regression analysis revealed that the inattention item on the QuENA and orientation item on the CASI had independent effects on the GL incidence, while the absence of a safety range was associated with the risk of GL recurrence. During the 2.5 years, the PwAD with GL incidence deteriorated more in the mental manipulation item on the CASI than those without. We suggest that before the occurrence of GL, the caregivers of PwAD should refer to the results of cognitive assessment and navigation ability evaluation to enhance the orientation and attention of the PwAD. Once GL occurs, the caregivers must set a safety range to prevent GL recurrence, especially for younger people.
    Full-text · Article · May 2016
    • "a b Distinct cortical differences were not observed for b-amyloid burden between AD subtypes, although NFTD had significantly lower burden compared to all AD subtypes . Minimal cortical b-amyloid pathology is consistent with previous descriptions of NFTD [3, 5, 17, 18, 20, 21, 31], where neuritic type SPs were absent and SPs that were present had characteristics of diffuse b-amyloid deposits. APOE e4 status has been shown to influence plaque density [16], but this alone does not explain the lack of SPs in NFTD. "
    [Show abstract] [Hide abstract] ABSTRACT: Alzheimer's disease (AD) can be classified based on the relative density of neurofibrillary tangles (NFTs) in the hippocampus and association cortices into three subtypes: typical AD, hippocampal-sparing AD (HpSp AD), and limbic-predominant AD (LP AD). AD subtypes not only have pathologic, but also demographic, clinical, and genetic differences. Neurofibrillary tangle-predominant dementia (NFTD), a disorder with NFTs relatively restricted to limbic structures, shares this feature with LP AD raising the possibility that NFTD is a variant of AD. The objective criteria for pathologic diagnosis of NFTD are not available. A goal of this study was to design a mathematical algorithm that could diagnose NFTD from NFT and senile plaque (SP) counts in hippocampus and association cortices, analogous to that used to subtype AD. Moreover, we aimed to compare pathologic, demographic, clinical, and genetic features of NFTD (n = 18) with LP AD (n = 19), as well as the other AD subtypes, typical AD (n = 52) and HpSp AD (n = 17). Using digital microscopy, we confirmed that burden of phospho-tau (CP13) and of an NFT conformational epitope (Ab39) correlated with NFT densities and showed expected patterns across AD subtypes. HpSp AD had the highest and LP AD had the lowest burden of cortical CP13 and Ab39 immunoreactivity. On the other hand, cortical β-amyloid burden did not significantly differ between AD subtypes. Semi-quantitative assessment of SPs in the basal ganglia did show HpSp AD to have significantly more frequent presence of SPs compared to typical AD, which was more frequent than LP AD. Compared to LP AD, NFTD had an older age at disease onset and shorter disease duration, as well as lower Braak NFT stage. NFTs and SPs on thioflavin-S fluorescent microscopy, as well as CP13, Ab39, and Aβ immunoreactivities were very low in the frontal cortex of NFTD, differentiating NFTD from AD subtypes, including LP AD. MAPT H1H1 genotype frequency was high (~70 %) in NFTD and LP AD, and similar to typical AD, while APOE ε4 carrier state was low in NFTD. While it shares clinical similarities with regard to female sex predominance, onset in advanced age, and a slow cognitive decline, NFTD has significant pathologic differences from LP AD, suggesting that it may not merely be a variant of AD.
    Full-text · Article · Sep 2012
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