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Average aging is associated with a gradual decline of memory capacity. SuperAgers are humans ≥80 years of age who show exceptional episodic memory at least as good as individuals 20-30 years their junior. This study investigated whether neuronal integrity in the entorhinal cortex (ERC), an area critical for memory and selectively vulnerable to neurofibrillary degeneration, differentiated SuperAgers from cognitively healthy younger individuals, cognitively average peers ("Normal Elderly"), and individuals with amnestic mild cognitive impairment. Postmortem sections of the ERC were stained with cresyl violet to visualize neurons and immunostained with mouse monoclonal antibody PHF-1 to visualize neurofibrillary tangles. The crosssectional area (i.e., size) of layer II and layer III/V ERC neurons were quantified. Two-thirds of total participants were female. Unbiased stereology was used to quantitate tangles in a subgroup of SuperAgers and Normal Elderly. Linear mixedeffect models were used to determine differences across groups. Quantitative measurements found that the soma size of layer II ERC neurons in postmortem brain specimens were significantly larger in SuperAgers compared with all groups (p,0.05)--including younger individuals 20-30 years their junior (p<0.005). SuperAgers had significantly fewer stereologically quantified Alzheimer's disease-related neurofibrillary tangles in layer II ERC than Normal Elderly (p<0.05). This difference in tangle burden in layer II between SuperAgers and Normal Elderly suggests that tangle-bearing neurons may be prone to shrinkage during aging. The finding that SuperAgers show ERC layer II neurons that are substantially larger even compared with individuals 20-30 years younger is remarkable, suggesting that layer II ERC integrity is a biological substrate of exceptional memory in old age. [ABSTRACT FROM AUTHOR]

This human study is based on an established cohort of "SuperAgers," 80+-year-old individuals with episodic memory function at a level equal to, or better than, individuals 20-30 years younger. A preliminary investigation using structural brain imaging revealed a region of anterior cingulate cortex that was thicker in SuperAgers compared with healthy 50- to 65-year-olds. Here, we investigated the in vivo structural features of cingulate cortex in a larger sample of SuperAgers and conducted a histologic analysis of this region in postmortem specimens. A region-of-interest MRI structural analysis found cingulate cortex to be thinner in cognitively average 80+ year olds (n = 21) than in the healthy middle-aged group (n = 18). A region of the anterior cingulate cortex in the right hemisphere displayed greater thickness in SuperAgers (n = 31) compared with cognitively average 80+ year olds and also to the much younger healthy 50-60 year olds (p < 0.01). Postmortem investigations were conducted in the cingulate cortex in five SuperAgers, five cognitively average elderly individuals, and five individuals with amnestic mild cognitive impairment. Compared with other subject groups, SuperAgers showed a lower frequency of Alzheimer-type neurofibrillary tangles (p < 0.05). There were no differences in total neuronal size or count between subject groups. Interestingly, relative to total neuronal packing density, there was a higher density of von Economo neurons (p < 0.05), particularly in anterior cingulate regions of SuperAgers. These findings suggest that reduced vulnerability to the age-related emergence of Alzheimer pathology and higher von Economo neuron density in anterior cingulate cortex may represent biological correlates of high memory capacity in advanced old age. [ABSTRACT FROM AUTHOR]

Primary progressive aphasia (PPA) is a neurodegenerative syndrome that causes a gradual atrophy of the left hemisphere language network, leading to impairments of object naming (anomia) and word comprehension. In 33 human subjects with PPA, object naming and word comprehension were explored with N400 potentials elicited by picture-word or picture-picture matching tasks. Two mechanisms of impairment were identified. In one group of patients, where the object name could be recognized but not retrieved during verbal naming, N400s in picture-word trials were also abnormal, revealing an associative basis for retrieval anomia. In these patients, a putative prephonological signal (i.e., lemma) evoked by the object picture appears to have become too weak to elicit retrieval, but not necessarily too weak to support the informationally less taxing process of recognition. A second group of PPA patients showed more severe naming deficits--the object name was neither verbalized nor recognized. Furthermore, nouns of the same category (but not those of other object categories) could not be identified as mismatches. This blurring of intracategory but not intercategory differentiation of word meaning was correlated with anterior temporal atrophy, predominantly in the left hemisphere, especially along the superior temporal gyrus. Although not part of the classic language network, this area appears critical for proceeding from generic to specific levels of word comprehension and object naming. N400 abnormalities emerged for lexical (picture-word) but not nonverbal (picture-picture) associations, supporting a dual-route rather than amodal organization of object concepts. [ABSTRACT FROM AUTHOR]

Primary progressive aphasia (PPA) is a clinical dementia syndrome characterized by progressive decline in language function but relative sparing of other cognitive domains. There are three recognized PPA variants: agrammatic, semantic, and logopenic. Although each PPA subtype is characterized by the nature of the principal deficit, individual patients frequently display subtle impairments in additional language domains. The present study investigated the distribution of atrophy related to performance in specific language domains (i.e., grammatical processing, semantic processing, fluency, and sentence repetition) across PPA variants to better understand the anatomical substrates of language. Results showed regionally specific relationships, primarily in the left hemisphere, between atrophy and impairments in language performance. Most notable was the neuroanatomical distinction between fluency and grammatical processing. Poor fluency was associated with regions dorsal to the traditional boundaries of Broca's area in the inferior frontal sulcus and the posterior middle frontal gyrus, whereas grammatical processing was associated with more widespread atrophy, including the inferior frontal gyrus and supramarginal gyrus. Repetition performance was correlated with atrophy in the posterior superior temporal gyrus. The correlation of atrophy with semantic processing impairment was localized to the anterior temporal poles. Atrophy patterns were more closely correlated with domain-specific performance than with subtype. These results show that PPA reflects a selective disruption of the language network as a whole, with no rigid boundaries between subtypes. Further, these atrophy patterns reveal anatomical correlates of language that could not have been surmised in patients with aphasia resulting from cerebrovascular lesions. [ABSTRACT FROM AUTHOR]