Cortical and Hippocampal Atrophy in Patients with Autosomal Dominant Familial Alzheimer’s Disease

Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology, UCLA School of Medicine, Los Angeles, Calif., USA.
Dementia and Geriatric Cognitive Disorders (Impact Factor: 3.55). 09/2011; 32(2):118-25. DOI: 10.1159/000330471
Source: PubMed


Both familial and sporadic Alzheimer's disease (AD) result in progressive cortical and subcortical atrophy. Familial autosomal dominant AD (FAD) allows us to study AD brain changes presymptomatically.
33 subjects at risk for FAD (25 for PSEN1 and 8 for APP mutations; 22 mutation carriers and 11 controls) and 3 demented PSEN1 mutation carriers underwent T(1)-weighted MPRAGE 1.5T MRI. Using the hippocampal radial distance and cortical pattern matching techniques, we investigated the effects of carrier status and dementia diagnosis on cortical and hippocampal atrophy. All analyses were corrected for age and relative age (years to median age of disease onset in the family).
The dementia cases had pronounced cortical atrophy in the lateral and medial parietal, posterior cingulate and frontal cortices and hippocampal atrophy bilaterally relative to both nondemented carriers and controls. Nondemented carriers did not show significant cortical thinning or hippocampal atrophy relative to controls.
FAD is associated with thinning of the posterior association and frontal cortices and hippocampal atrophy. Larger sample sizes may be necessary to reliably identify cortical atrophy in presymptomatic carriers.

Download full-text


Available from: Paul Thompson, Oct 06, 2015
41 Reads
  • Source
    • "Gray matter regional volume loss and decreases in magnetization transfer ratio have also been reported in mildly symptomatic carriers [69]. Additionally, it has been well established that in early onset AD, hippocampus may be not always involved as in the typical form and that frontoparietal areas showed greater atrophy in monogenic forms compared with sporadic late onset cases [68, 70, 71]. APP mutations seem to be more associated with hippocampal atrophy, whereas PSEN1 mutation carriers had more general neocortical involvement and a prominent frontotemporal atrophy [68, 72]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The discovery of monogenic forms of Alzheimer's Disease (AD) associated with mutations within PSEN1, PSEN2, and APP genes is giving a big contribution in the understanding of the underpinning mechanisms of this complex disorder. Compared with sporadic form, the phenotype associated with monogenic cases is somewhat broader including behavioural disturbances, epilepsy, myoclonus, and focal presentations. Structural and functional imaging show typical early changes also in presymptomatic monogenic carriers. Amyloid imaging and CSF tau/A β ratio may be useful in the differential diagnosis with other neurodegenerative dementias, especially, in early onset cases. However, to date any specific biomarkers of different monogenic cases have been identified. Thus, in clinical practice, the early identification is often difficult, but the copresence of different elements could help in recognition. This review will focus on the clinical and instrumental markers useful for the very early identification of AD monogenic cases, pivotal in the development, and evaluation of disease-modifying therapy.
    11/2013; 2013(6543):689591. DOI:10.1155/2013/689591
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Biological markers of utility in tracking Alzheimer's disease (AD) during the presymptomatic prodromal phase are important for prevention studies. Changes in cerebrospinal fluid (CSF) levels of 42-amino-acid β-amyloid (Aβ(42)), total tau protein (t-tau) and phosphorylated tau at residue 181 (p-tau(181)) during this state are incompletely characterized. We measured CSF markers in 13 carriers of familial AD (FAD) mutations that are fully penetrant for causing AD (PSEN1 and APP) and in 5 non-mutation-carrying family members. Even among the entirely presymptomatic mutation carriers (n = 9), Aβ(42) was diminished (388.7 vs. 618.4 pg/ml, p = 0.004), and t-tau (138.5 vs. 50.5 pg/ml, p = 0.002) and p-tau(181) (71.7 vs. 24.6 pg/ml, p = 0.003) were elevated. There was a negative correlation between Aβ(42) levels and age relative to the family-specific age of dementia diagnosis. Our data are consistent with a decline in CSF Aβ(42) levels occurring at least 20 years prior to clinical dementia in FAD.
    Dementia and Geriatric Cognitive Disorders 02/2012; 33(1):1-5. DOI:10.1159/000335729 · 3.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Early-onset Alzheimer's disease (EOAD) is generally thought to have a more rapid course compared to late-onset Alzheimer's disease (LOAD). The faster progression of EOAD observed in some studies has also been thought to correlate with cerebrospinal fluid (CSF) biomarkers. Our clinical experience has not been suggestive of any difference in disease progression; therefore, we decided to investigate whether differences in clinical progression and CSF biomarkers between EOAD and LOAD could be demonstrated. Case-control study with 42 patients, 21 EOAD and 21 matched LOAD patients. Rates of progression were calculated and these, as well as CSF biomarker levels, were statistically compared. There were no statistically significant differences in clinical progression between the EOAD group and the LOAD group. There was no significant difference in the absolute values of CSF biomarkers, but a tendency towards lower levels of β-amyloid in patients with EOAD was observed. Our findings did not converge with results from the majority of previous studies, which have been suggestive of a faster clinical progression in EOAD. Possibly, the very strict algorithm by which our patients were matched explains our findings. However, the findings should be repeated in a larger study population.
    Dementia and Geriatric Cognitive Disorders 04/2012; 33(2-3):111-7. DOI:10.1159/000337386 · 3.55 Impact Factor
Show more