Progression of Atrophy in Alzheimer’s Disease and Related Disorders

Abstract

Longitudinal MRI is a powerful tool that allows the assessment of progression of brain changes over multiple imaging time-points and has been increasingly employed in the study of neurodegenerative dementias, particularly Alzheimer's disease (AD). Early studies demonstrated that AD was associated with increased rates of whole brain loss and hippocampal atrophy. A number of sophisticated voxel-level techniques have now been developed that have provided additional information describing regional atrophy over time in the temporal, parietal, and frontal lobes in AD. Studies have also focused on subjects in the prodromal phase of AD in order to describe the earliest changes that are occurring in the brain. Atrophy has been shown to start in the medial temporal lobes and fusiform gyrus at least 3 years before subjects reach a diagnosis of AD, and then spread to the posterior temporal lobes and parietal lobes, and then eventually the frontal lobes. These patterns of atrophy correlate well with the progression of neurofibrillary tangles observed on pathology. Rates of atrophy have also been shown to accelerate over the course of the disease as a subject progresses from cognitively normal to a diagnosis of AD. Similar techniques have also been applied to other neurodegenerative diseases, such as frontotemporal dementia which show higher rates of atrophy and different patterns of progression to those observed in AD. Hence, longitudinal MRI shows promise as a biomarker of disease progression in neurodegenerative disease.

Epigenetic regulation of estrogen-dependent memory

“…The rationale for the field’s preoccupation with the hippocampus likely results, in part, because it was the first “cognitive” region of the rodent brain in which hormonal regulation of neuronal morphology was documented. Interest in the hippocampus has also been guided by numerous other factors, including: (1) it is essential for the formation of many types of memories, (2) is it one of the earliest brain regions to deteriorate in Alzheimer’s disease, and (3) hippocampal dysfunction is implicated in memory loss associated with aging, neurodegenerative diseases (e.g., Alzheimer’s disease, Parkinson’s disease, multiple sclerosis), and neuropsychiatric diseases (e.g., schizophrenia, depression) (Chiaravalloti and DeLuca, 2008; Whitwell, 2010; Ferreira et al, 2011; Holtzman et al, 2011; Kooi et al, 2011; Small et al, 2011). Nevertheless, effects of estrogens on other cognitive regions of the brain have been reported, most notably in the prefrontal cortex and amygdala (Tang et al, 2004; Inagaki et al, 2010).…”

The use of metacognitive strategies to decrease false memories in source monitoring in patients with mild cognitive impairment

“…The AD pathophysiological process is thought to initially cause destruction to the medial temporal lobes along with other areas of the temporo-parietal region. As AD patients progress from mild cognitive impairment to very mild, mild, and moderate dementia stages, the disease causes increased destruction to lateral temporal, parietal, and later, frontal lobes (Apostolova et al, 2006; Braskie, Toga, & Thompson, 2013; Scahill, Schott, Stevens, Rossor, & Fox, 2002; Whitwell et al, 2007; Whitwell, 2010). Based on this pathological progression and prior findings that executive functioning is less impaired in MCI compared to AD (Carter, Caine, Burns, Herholz, & Lambon Ralph, 2012), patients with MCI may be more able to use strategies to boost source memory compared to individuals with more advanced disease.…”

Mapping the Progression of Atrophy in Early- and Late-Onset Alzheimer’s Disease

“…In the early nineties, Braak and Braak conducted the first pathological studies to identify the trajectory of neurodegeneration in AD [22, 23]. In the last decades, imaging studies have investigated in vivo the progression of atrophy in LOAD, showing a spreading of the pathology through a widespread pattern including medial and lateral temporal, frontal, and parietal lobes bilaterally, with maximal differences found in the left medial temporal regions [24] (see for a review [25]). To our knowledge, only one study has assessed atrophy progression in EO relative to LOAD so far showing more rapid decline and more rapid cortical thinning in widespread association cortices in EOAD group [26].…”