. Hippocampal mean diffusivity and memory in healthy elderly individuals: a cross-sectional study. Neurology. 2010 Jan 19;74(3):194-200. PubMed.

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  1. This recent article by Carlesimo et al. lends support to the idea that
    diffusion tensor imaging (DTI) may be a more sensitive predictor of
    disease than conventional T1-weighted MRI. Carlesimo et al. found that measures of hippocampal diffusion, but not volume, were associated with memory function in people middle and older aged. The individuals in the present study were healthy, but as higher diffusion was associated with lower memory performance, the data suggest that DTI may be sensitive to diseases such as Alzheimer’s that affect memory performance and other cognitive functions.

    Carlesimo et al. did not have information on ApoE or other risk factors
    for AD. Recently we showed that risk for AD among healthy late
    middle-aged adults was associated with hippocampal alteration as
    detected by DTI but not T1-weighted imaging (Bendlin et al., 2009, in
    press, Alzheimer’s and Dementia). Specifically, parental family
    history was associated with altered anisotropic diffusion in the
    hippocampus. The effect of ApoE was additive, whereby presence of both
    family history and ApoE4 genotype was associated with greatest
    hippocampal alteration.

    The findings from Carlesimo et al. also highlight a drawback of
    conventional T1-weighted 3D scans. The T1 volume has been the sequence
    of choice for volumetric brain studies over the last 15 years, and from
    it, scientists have learned a great deal about hippocampal volume in AD,
    MCI, and aging. However, the sequence by its nature is not very sensitive
    to pathophysiological processes. Thus, in some ways it is not too
    surprising that a more sensitive type of scan showed a greater
    relationship to memory function in ostensibly healthy older adults.

    DTI also has its limitations, including resolution and measurement
    variability. Further longitudinal work will be needed to determine the
    clinical utility of DTI in characterizing the profile of individuals who
    will ultimately progress to disease, a profile that will likely consist
    of several key indicators including family history, genotype, CSF
    markers, and sensitive imaging.

  2. This article by Carlesimo and colleagues highlights the important role that neuroimaging measures may play in the detection of individuals in the early stages of neurodegenerative cognitive disorders of aging, such as Alzheimer disease. In particular, this study found that mean diffusivity (MD) of the left hippocampus, a microscopic measure of random water molecule movement derived from diffusion tensor imaging (DTI), was predictive of performance on two measures of memory in cognitively normal adults over the age of 50. Other brain measures, including hippocampal volume, were not associated with memory performance.

    An important consideration that is also brought to light by the findings in this article is that of the measurement of memory itself. Memory is a construct that is only as useful as the cognitive assessments that represent it. In the context of a cross-sectional study, the cognitive test chosen to characterize early Alzheimer disease should be both sensitive to dysfunction and specific to the disease. We recently reported (1) findings from the Einstein Aging Study that described both hippocampal volume and metabolism as independent predictors of performance on the Free and Cued Selective Reminding Test (FCSRT) in older adults with normal memory abilities and mild memory impairment. The FCSRT differs from other measures of verbal memory in that it utilizes a controlled-learning paradigm to focus attention and provide cue-based strategies such that maximal learning and recall of information may occur. FCSRT performance has been shown to have high discriminative validity for the diagnosis of dementia (e.g., see [2]) and for prediction of the development of future dementia (3).

    Thus, the lack of a cross-sectional relationship between a neuroimaging measure and a memory measure may be more reflective of the appropriateness of the assessments rather than the validity of an underlying brain-behavior relationship. As researchers continue to devote their efforts toward identifying older adults at the earliest stages of Alzheimer disease, an essential consideration will be the selection and development of both neuroimaging and memory measures that are sensitive and specific to the disease.

    References:

    . Hippocampal neurochemistry, neuromorphometry, and verbal memory in nondemented older adults. Neurology. 2008 Apr 29;70(18):1594-600. Epub 2008 Mar 26 PubMed.

    . Sensitivity to semantic cuing: an index of episodic memory dysfunction in early Alzheimer disease. Alzheimer Dis Assoc Disord. 1999 Jan;13(1):38-46. PubMed.

    . Memory impairment on free and cued selective reminding predicts dementia. Neurology. 2000 Feb 22;54(4):827-32. PubMed.