Long-Term Perseveration in Alzheimer’s Disease: A Case Report

The most common clinical sign of Alzheimer's disease (AD) is progressive memory loss. Presented here is a case of AD who, despite ultimate profound dementia with severe amnesia, showed retention of a perseverative response she developed during 26 encounters, over 4.5 years, with the Brown–Peterson distractor test. From Test 9 onwards, she responded from the first distractor-filled trial with one consonant trigram, appearing in none of the seven test forms given her. At Test 26, she could not repeat heard trigrams yet faithfully responded with her perseverative trigram. The trigram, ostensibly declarative information, apparently became part and parcel of the task's procedure. Although perseveration is a form of impairment probably resulting from Alzheimer pathology involving frontal and parietal cortex, it may also reflect a form of preserved memory, albeit distorted, supported by posterior cortical regions spared in AD

Autobiographical Memory in Normal Ageing and Dementia

Autobiographical memories in young and elderly normal subjects are drawn mostly from the recent past but elderly subjects relate a second peak of memories from early adulthood. Memory for remote past public events is relatively preserved in dementia, possibly reflecting integrity of semantic relative to episodic memory. We examined recall of specific, consistent autobiographical episodes in Alzheimer's disease (AD) in response to cue words. Patients and control subjects drew most memories from the recent 20 years: episode age related to anterograde memory function but not subject age or dementia. Subjects also related a secondary peak of memories from early adulthood; episode age related to subject age and severity of dementia. The results suggest that preferential recall of memories from early adulthood is based on the salience of retrieval cues, altered by age and dementia, superimposed on a temporal gradient of semantic memory. Further, AD shows behavioural similarity to normal ageing

MRI estimates of brain iron concentration in normal aging: Comparison of field-dependent (FDRI) and phase (SWI) methods

Different brain structures accumulate iron at different rates throughout the adult life span. Typically, striatal and brain stem structures are higher in iron concentrations in older than younger adults, whereas cortical white matter and thalamus have lower concentrations in the elderly than young adults. Brain iron can be measured in vivo with MRI by estimating the relaxivity increase across magnetic field strengths, which yields the Field-Dependent Relaxation Rate Increase (FDRI) metric. The influence of local iron deposition on susceptibility, manifests as MR phase effects, forms the basis for another approach for iron measurement, Susceptibility-Weighted Imaging (SWI), for which imaging at only one field strength is sufficient. Here, we compared the ability of these two methods to detect and quantify brain iron in 11 young (5 men, 6 women; 21 to 29 years) and 12 elderly (6 men, 6 women; 64 to 86 years) healthy adults. FDRI was acquired at 1.5 T and 3.0 T, and SWI was acquired at 1.5 T. The results showed that both methods detected high globus pallidus iron concentration regardless of age and significantly greater iron in putamen with advancing age. The SWI measures were more sensitive when the phase signal intensities themselves were used to define regions of interest, whereas FDRI measures were robust to the method of region of interest selection. Further, FDRI measures were more highly correlated than SWI iron estimates with published postmortem values and were more sensitive than SWI to iron concentration differences across basal ganglia structures. Whereas FDRI requires more imaging time than SWI, two field strengths, and across-study image registration for iron concentration calculation, FDRI appears more specific to age-dependent accumulation of non-heme brain iron than SWI, which is affected by heme iron and non-iron source effects on phase.National Institutes of Health (U.S.) (Grant AG017919)National Institutes of Health (U.S.) (Grant AA005965)National Institutes of Health (U.S.) (Grant AA017168

MRI estimates of brain iron concentration in normal aging using quantitative susceptibility mapping

Quantifying tissue iron concentration in vivo is instrumental for understanding the role of iron in physiology and in neurological diseases associated with abnormal iron distribution. Herein, we use recently-developed Quantitative Susceptibility Mapping (QSM) methodology to estimate the tissue magnetic susceptibility based on MRI signal phase. To investigate the effect of different regularization choices, we implement and compare ℓ[subscript 1] and ℓ[subscript 2] norm regularized QSM algorithms. These regularized approaches solve for the underlying magnetic susceptibility distribution, a sensitive measure of the tissue iron concentration, that gives rise to the observed signal phase. Regularized QSM methodology also involves a pre-processing step that removes, by dipole fitting, unwanted background phase effects due to bulk susceptibility variations between air and tissue and requires data acquisition only at a single field strength. For validation, performances of the two QSM methods were measured against published estimates of regional brain iron from postmortem and in vivo data. The in vivo comparison was based on data previously acquired using Field-Dependent Relaxation Rate Increase (FDRI), an estimate of MRI relaxivity enhancement due to increased main magnetic field strength, requiring data acquired at two different field strengths. The QSM analysis was based on susceptibility-weighted images acquired at 1.5 T, whereas FDRI analysis used Multi-Shot Echo-Planar Spin Echo images collected at 1.5 T and 3.0 T. Both datasets were collected in the same healthy young and elderly adults. The in vivo estimates of regional iron concentration comported well with published postmortem measurements; both QSM approaches yielded the same rank ordering of iron concentration by brain structure, with the lowest in white matter and the highest in globus pallidus. Further validation was provided by comparison of the in vivo measurements, ℓ[subscript 1]-regularized QSM versus FDRI and ℓ[subscript 2]-regularized QSM versus FDRI, which again yielded perfect rank ordering of iron by brain structure. The final means of validation was to assess how well each in vivo method detected known age-related differences in regional iron concentrations measured in the same young and elderly healthy adults. Both QSM methods and FDRI were consistent in identifying higher iron concentrations in striatal and brain stem ROIs (i.e., caudate nucleus, putamen, globus pallidus, red nucleus, and substantia nigra) in the older than in the young group. The two QSM methods appeared more sensitive in detecting age differences in brain stem structures as they revealed differences of much higher statistical significance between the young and elderly groups than did FDRI. However, QSM values are influenced by factors such as the myelin content, whereas FDRI is a more specific indicator of iron content. Hence, FDRI demonstrated higher specificity to iron yet yielded noisier data despite longer scan times and lower spatial resolution than QSM. The robustness, practicality, and demonstrated ability of predicting the change in iron deposition in adult aging suggest that regularized QSM algorithms using single-field-strength data are possible alternatives to tissue iron estimation requiring two field strengths.National Institutes of Health (U.S.) (Grant NIH R01 EB007942)National Institutes of Health (U.S.) (Grant AG019717)National Institutes of Health (U.S.) (Grant AA005965)National Institutes of Health (U.S.) (Grant AA017168)National Institutes of Health (U.S.) (Grant EB008381)National Science Foundation (U.S.) (Grant 0643836)Siemens CorporationSiemens-MIT AllianceMIT-Center for Integration of Medicine and Innovative Technology (Medical Engineering Fellowship

Quantitative Susceptibility Mapping by Inversion of a Perturbation Field Model: Correlation With Brain Iron in Normal Aging

There is increasing evidence that iron deposition occurs in specific regions of the brain in normal aging and neurodegenerative disorders such as Parkinson's, Huntington's, and Alzheimer's disease. Iron deposition changes the magnetic susceptibility of tissue, which alters the MR signal phase, and allows estimation of susceptibility differences using quantitative susceptibility mapping (QSM). We present a method for quantifying susceptibility by inversion of a perturbation model, or “QSIP.” The perturbation model relates phase to susceptibility using a kernel calculated in the spatial domain, in contrast to previous Fourier-based techniques. A tissue/air susceptibility atlas is used to estimate B[subscript 0] inhomogeneity. QSIP estimates in young and elderly subjects are compared to postmortem iron estimates, maps of the Field-Dependent Relaxation Rate Increase, and the L1-QSM method. Results for both groups showed excellent agreement with published postmortem data and in vivo FDRI: statistically significant Spearman correlations ranging from Rho=0.905 to Rho=1.00 were obtained. QSIP also showed improvement over FDRI and L1-QSM: reduced variance in susceptibility estimates and statistically significant group differences were detected in striatal and brainstem nuclei, consistent with age-dependent iron accumulation in these regions.National Institutes of Health (U.S.) (Grant P41EB015902)National Institutes of Health (U.S.) (Grant P41RR013218)National Institutes of Health (U.S.) (Grant P41EB015898)National Institutes of Health (U.S.) (Grant P41RR019703)National Institutes of Health (U.S.) (Grant T32EB0011680-06)National Institutes of Health (U.S.) (Grant K05AA017168)National Institutes of Health (U.S.) (Grant R01AA012388