Distinct MRI Atrophy Patterns in Autopsy-Proven Alzheimer's Disease and Frontotemporal Lobar Degeneration

Memory and Aging Center, University of California, San Francisco, California 94143, USA.
American Journal of Alzheimer s Disease and Other Dementias (Impact Factor: 1.63). 12/2008; 22(6):474-88. DOI: 10.1177/1533317507308779
Source: PubMed


To better define the anatomic distinctions between Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD), we retrospectively applied voxel-based morphometry to the earliest magnetic resonance imaging scans of autopsy-proven AD (N = 11), FTLD (N = 18), and controls (N = 40). Compared with controls, AD patients showed gray matter reductions in posterior temporoparietal and occipital cortex; FTLD patients showed atrophy in medial prefrontal and medial temporal cortex, insula, hippocampus, and amygdala; and patients with both disorders showed atrophy in dorsolateral and orbital prefrontal cortex and lateral temporal cortex (P(FWE-corr) < .05). Compared with FTLD, AD patients had decreased gray matter in posterior parietal and occipital cortex, whereas FTLD patients had selective atrophy in anterior cingulate, frontal insula, subcallosal gyrus, and striatum (P < .001, uncorrected). These findings suggest that AD and FTLD are anatomically distinct, with degeneration of a posterior parietal network in AD and degeneration of a paralimbic fronto-insular-striatal network in FTLD.

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Available from: Stephen C Allison, May 20, 2014
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    • "Regardless of the presence of concomitant ALS (Lillo et al., 2010), the progressive deterioration in behavior and personality in bvFTD (Rascovsky et al., 2011) has been largely attributed to degeneration in the prefrontal, insular and temporal cortices (Rabinovici et al., 2007; Seeley et al., 2008). These cortical regions are known to demonstrate dense reciprocal connections with the cerebellum (Middleton and Strick, 2000, 2001; O'Reilly et al., 2010) and we recently confirmed that the degeneration of particular cerebellar subregions impacts on the overall cognitive and neuropsychiatric performances in bvFTD (Tan et al., 2014). "
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    ABSTRACT: Although converging evidence has positioned the human cerebellum as an important relay for intact cognitive and neuropsychiatric processing, changes in this large structure remain mostly overlooked in behavioral variant frontotemporal dementia (bvFTD), a disease which is characterized by cognitive and neuropsychiatric deficits. The present study assessed whether degeneration in specific cerebellar subregions associate with indices of cognition and neuropsychiatric performance in bvFTD. Our results demonstrate a relationship between cognitive and neuropsychiatric decline across various domains of memory, language, emotion, executive, visuospatial function, and motivation and the degree of gray matter degeneration in cerebellar lobules V-VII. Most notably, bilateral cerebellar lobule VII and the posterior vermis emerged as distinct for memory processes, the right cerebellar hemisphere underpinned emotion, and the posterior vermis was highlighted in language dysfunction in bvFTD. Based on cortico-cerebellar connectivity maps, these findings in the cerebellum are consistent with the neural connections with the cortices involved in these domains in patients with bvFTD. Overall, the present study underscores the significance of cortical-cerebellar networks associated with cognition and neuropsychiatric dysfunction in bvFTD.
    Frontiers in Aging Neuroscience 07/2015; 7:121. DOI:10.3389/fnagi.2015.00121 · 4.00 Impact Factor
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    • "the associated frontal circuit in comparison to other neurodegenerative conditions (Rabinovici et al., 2007). Grossman et al. (2010) examined the interpretation of positive and negative situations in individuals with bvFTD and found that these individuals were particularly impaired in interpreting negative consequences of a social situation (e.g., " rolling through a red light at 2 a.m. when there is a police car at the intersection , " p. 5). "
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    ABSTRACT: Apathy, a reduction in goal-directed behavior (GDB), affects 90% of individuals with behavioral variant frontotemporal degeneration, which is a common cause of early onset neurodegenerative disease. The cognitive and neural impairments associated with apathy make it difficult to initiate, plan, and self-motivate activities toward a specific goal, such as dressing or bathing. These impairments are associated with significant decline in functional ability, caregiver burden, and increased cost of care due to early institutionalization. The current article reviews the evidence suggesting that apathy arises from the interruption of one or any combination of three GDB processes: initiation, planning, and motivation. From this perspective, three subtypes of apathy related to dysfunction at the level of GDB and the corresponding neuroanatomy are explored. Further research is required to confirm and measure these subtypes of apathy for use in clinical and research settings. A more precise classification of apathy by subtype will allow implementation of the most appropriate person-centered, individualized therapy. [Journal of Gerontological Nursing, xx(x), xx-xx.].
    Journal of Gerontological Nursing 09/2014; 40(10):1-8. DOI:10.3928/00989134-20140827-01 · 1.02 Impact Factor
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    • "Aberrant projections from hippocampus and/or MTL could influence frontal cortex function prior to ADrelated anatomical changes. Pathology in mild AD is thought to be limited to the temporo-parietal junction (Rabinovici et al., 2007), which does not include the PEFs, so a lack of impairment in prosaccade generation is not surprising. It has been shown previously that volumetric changes in the SEF correlate with antisaccade latency, but that DLPFC and FEF volume were not correlated with antisaccade performance (Boxer et al., 2006), supporting the notion that functional changes probably precede anatomical changes in the frontal cortex of AD patients. "
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    ABSTRACT: Alzheimer's disease (AD) is a disorder of progressive memory loss and executive dysfunction. Little is known about the progression from amnestic mild cognitive impairment (aMCI; isolated memory loss) to AD. Studies have found impairments in mild-stage AD and aMCI in specific tests of executive function. Here, we used objective saccade tasks to determine if they can effectively assess executive function deficits otherwise assessed by neuropsychological testing. To determine which executive function deficits the saccade tasks are most sensitive to, we also investigated the relationship between performance on saccade tasks and neuropsychological test scores. Twenty-two aMCI patients (63-90years), 24 mild AD patients (61-87years) and 76 healthy controls (60-85years) performed a battery of neuropsychological tests, and two saccade tasks designed to probe sensory, motor and cognitive function. The prosaccade task requires a fast, automatic saccade toward an eccentric visual stimulus. The antisaccade task requires additional executive processing to inhibit the automatic prosaccade toward the stimulus, so that a voluntary saccade can be initiated to a location opposite the stimulus. Antisaccade performance was impaired similarly in aMCI and AD patients relative to controls; both groups were slower to initiate correct antisaccades and they made more direction errors (erroneous prosaccades), suggesting similar brain deficits. Scores on the Stroop task were inversely correlated with the percentage of short-latency direction errors in the antisaccade task for controls and aMCI patients, whereas other more global measures of executive function were not related to saccade measures in any subject group. Our results show that the antisaccade task is useful for detecting executive dysfunction in aMCI and AD, especially dysfunction in selective attention. Saccade tasks may therefore have potential to assess executive dysfunction when use of neuropsychological tests is not possible.
    European Journal of Neuroscience 06/2014; 39(11). DOI:10.1111/ejn.12617 · 3.18 Impact Factor
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