. Rates of decline in Alzheimer disease decrease with age. PLoS One. 2012;7(8):e42325. PubMed.


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  1. The paper by Dominic Holland et al. reporting that AD-associated decline slows with advancing age is interesting. Although no autopsy confirmation was available in this study, these data agree with neuropathologic studies in the oldest-old (Haroutunian et al., 2008).

    However, there are some limitations of this study, which only in part have been mentioned by the authors:

    1. The importance of confounding pathologies, in particular, cerebrovascular lesions including the importance of CAA (the authors only mentioned microvascular pathology), Lewy body pathology, argyrophilic grain disease, hippocampal atrophy, etc., which are frequent in aged human brains (see "mixed dementia," e.g., Kovacs et al., 2008; Jellinger and Attems, 2011). It should be emphasized that up to two-thirds of aged human brains contain non-AD type pathologies (Nelson et al., 2007, and others).

    2. A high percentage of demented persons aged 80+ do not meet the morphological criteria of AD and are classified "dementia of unknown etiology" (Crystal et al., 1988; Jellinger, 2001; Corrada et al., 2012), which cannot be detected without morphological verification.

    In general, density and pattern of neurofibrillary tangles (NFTs) show significant correlations with the severity of cognitive decline across old age including 90+ patients, at least in those without other pathologies superimposed (Nelson et al., 2007; Nelson et al., 2010; Nelson et al., 2012).

    It should further be considered that there are several morphological subtypes of AD, which differ in age, duration, and dementia severity (Murray et al., 2011; Jellinger, 2012).

    All together, these and other data indicate that clinical detection of AD and its distinction from normal (and "pathological") aging—the latter featured by generalized Aβ deposition with only little tau pathology limited to the limbic areas—are more difficult in the oldest old, as stated by the authors.


    . A population-based clinicopathological study in the oldest-old: the 90+ study. Curr Alzheimer Res. 2012 Jul 1;9(6):709-17. PubMed.

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