A large body of research has investigated various aspects of attention in normal aging and Alzheimers disease (AD). Most of the previous studies have shown that divided attention, the ability to attend to two tasks or stimuli simultaneously, declines in both normal aging and AD. In a recent study of attention, Baddeley, Baddeley, Bucks, and Wilcock (2001) reported findings that contrast with other divided attention research. Specifically, they found no effects of aging on divided attention. Taken in combination with their findings of age and AD effects on other aspects of attention, the authors concluded that age-equivalent results on divided attention tasks support the theory that attentional control should be viewed as a fractionated system. Study 1 considered methodological differences between the divided attention tasks used by Baddeley et al., and the tasks used by researchers who have reported age-related differences. Specifically, the effects of task difficulty on age effects were examined. Young, middle-aged, and older adults were compared on a dual-task procedure that combined a secondary visuomotor task (box joining) with a primary verbal task (month reciting) administered at two levels of difficulty. Results showed a significant Age x Task Difficulty interaction. That is, differences among age groups were proportionately greater in the difficult dual-task condition versus the easy condition, suggesting that age-related declines in divided attention may only be detected if tasks are sufficiently difficult.<p> Study 2 examined attention in normal aging and AD. Young adults, older adults, and early-stage AD patients were compared on tasks of selective attention, focal attention, and divided attention, with each task administered at two levels of difficulty. Similar Group x Task Difficulty interaction effects were detected for all attentional tasks, a finding which is more consistent with a general-purpose model than a fractionated model of attention. Study 3 considered attentional tasks from a clinical perspective. Specifically, the attentional tasks utilized in Study 2 were examined with respect to their ability to correctly classify individuals with early-stage AD and normal older adults. Findings showed that all attentional tasks successfully discriminated patients from cognitively healthy older adults, with one task of divided attention showing particularly impressive sensitivity and specificity. Findings of the three studies are discussed with regard to their implications for future research and clinical practice.

Alzheimer’s disease (AD) progression and hypotheses of the cognitive reserve theory were investigated by testing for a relation between educational attainment and rate of decline in patients with Mild Cognitive Impairment, possible AD, probable AD, and other progressive neurodegenerative dementias. Patient data (n = 726) were acquired from a clinical database at the Minneapolis VAMC GRECC Memory Loss Clinic. Analyses using mixed effect regression models found education was significantly related to an accelerated rate of decline in global cognition (MMSE: -0.022, SE = 0.007, p = .003) and a steeper linear rate of decline in functional ability (Cognitive Performance Test: -0.034, SE = 0.011, p = .005). Cox proportional hazard models found little evidence to support an association between educational attainment and relative mortality risk. These results are consistent with previous findings and predictions of the cognitive reserve theory.

Thesis (Ph. D.)--University of California, San Diego and San Diego State University, 2003. / Vita. Includes bibliographical references (leaves 74-84).

Background: Research has demonstrated that adults with a moderate dementia can benefit from the introduction of a memory book to improve the quality of their conversational content. However, previous investigations in the area have focussed on low-tech alternative and augmentative communication aids. Few studies have investigated how digital media can be incorporated into therapy when working with people living with dementia. The present study addresses this gap in the literature by investigating the effects of a digital memory book on the quality and quantity of conversations in adults with mild to moderate dementia. Method: A single-subject multiple baseline design across behaviours with replication across four participants was used in this investigation. Four English speaking adults with a mild to moderate dementia and four of their family members participated in the study. The researcher developed a digital memory book using the Pictello™ application on an Apple iPad with the help of the participant and their family/whānau. Photos and statements were chosen in relation to these three conversational topics: Daily Life, Family, and Myself. During baseline and treatment sessions, the researcher met with each participant to conduct and record a five-minute conversation based on the three conversational topics. During treatment sessions, the researcher used the digital memory book to establish the effect of the memory book on the participants’ conversational utterances. Each conversation was transcribed verbatim by the researcher and analysed and coded for Memory Book Statements, Novel On-Topic Statements, Ambiguous Utterances, Unintelligible Utterances, Perseverative Utterances, Error Statements, Other Utterances, Partner Prompts, Partner Statements, Partner Questions, and Partner Other statements. A research assistant independently transcribed 20% of the transcripts and coded 20% of the conversations to establish the inter-observer agreement for the transcription and coding. Results: Visual analysis of the total-on-topic statements revealed a lack of evidence of a clear difference between the baseline and treatment phases across all the behaviours for each of the four participants. All four participants increased their total-on-topic statements with family members during an initial baseline session without the digital memory book to a follow-up session involving the digital memory book. Conclusion: Although the use of a digital memory book did not improve the quality and quantity of conversations in adults with mild to moderate dementia during conversations with the researcher, further research in the area is warranted. Future studies could focus on individuals with moderate or more severe dementia and individuals who are familiar with using digital media in their daily lives. Research could also focus more on the use of digital memory books during conversations with family members.

No description available.

The 5XFAD mouse is a double transgenic model of Alzheimer’s disease (AD), which harbors a human amyloid precursor protein transgene with three mutations (K670N/M671L, I716V, V717I) and a human presenilin-1 transgene with two mutations (M146L, L286V). These mutations act additively to produce large amounts of amyloid-beta (A?) and rapid development of AD-related pathology, including A?-plaques, neuroinflammation, synapse loss, impaired synaptic plasticity and death of layer 5 cortical neurons (Oakley et al., 2006, J. Neurosci., 26, 10129-10140). Despite the extensive characterization of neuropathology in the 5XFAD mouse, much less research has been completed characterizing age-related changes in behaviour. Sex, the albinism producing tyrosinase mutation (Tyrc), the retinal degeneration phosphodiesterase 6b mutation (Pde6brd1) and the limb-girdle muscular dystrophy 2B dysferlin mutation (Dysfim) are genetic factors present in the background strain (C57BLxSJL) of the 5XFAD mouse and other AD models. However, background genetic factors are rarely controlled, and their influence on AD-related behavioral phenotypes is largely unknown. Therefore, the objectives of this thesis were to characterize age-related changes in behaviour of the 5XFAD mouse, and determine the extent to which background genetic factors influence the expression of AD-related behavioral phenotypes. Male and female 5XFAD and wild-type (WT; C57BL6xSJL F2) mice completed a behavioural test battery at 3-4, 6-7, 9-10, 12-13 and 15-16 months of age in a cross-sectional experimental design. In experiment 1, motor ability was assessed with the open-field (locomotor activity), rota-rod (motor coordination and learning), balance beam (balance) and the wire and grid suspension tests (grip-strength). 5XFAD mice weighed less than WT mice at 9-15 months of age, and also reared less on the open-field and performed worse on the rota-rod. 5xFAD mice also travelled less distance on the open-field, fell faster on the balance beam and showed impaired grip-strength at 12-13 months of age. The Dysfim mutation has been previously shown to produce muscular weakness and impair motor function, but mutant Dysfim did not impair the motor performance of either WT or 5XFAD mice. In experiment 2, 5XFAD and WT mice were tested on the Morris water maze to assess visuo-spatial learning and memory. 5XFAD mice were impaired in acquisition and reversal learning, but not memory at 6 and 9 months of age. Motor impairments in 5XFAD mice impaired swimming ability and confounded learning and memory performance of mice at 12 and 15 months. Female mice performed worse than male mice, and albino mice performed worse than pigmented mice, demonstrating that background genetic factors influence the performance of mice on the Morris water maze. In experiment 3, olfactory learning and memory was assessed with an olfactory digging discrimination test. 5XFAD mice did not differ from WT mice in memory performance at any age tested. We then examined A? plaque pathology in 5XFAD mice and confirmed the presence of A? deposits in brain regions associated with motor function and learning and memory. Very few A? deposits were present in the cerebellum suggesting plaque pathology in the basal ganglia and/or motor cortex impairs motor function. Extensive A? plaque deposition was also found in the olfactory memory system despite the lack of olfactory memory impairment in 5XFAD mice. These results indicate that the 5XFAD mouse is a useful model for A?-pathology, cognitive and motor impairments observed in AD, but it is required that sex and albinism are properly controlled in the assessment of cognitive function.

Infrared microspectroscopy has been used to survey Alzheimer’s diseased brain tissue from a transgenic mouse model of the disease. Alzheimer’s disease is the leading cause of dementia among the elderly and is characterized by β-amyloid plaque deposition,neurofibrillary tangles, inflammation, and disturbed energy metabolism in the brain. Both the TgCRND8 and Tg19959 mouse models of the disease develop Alzheimer’s disease pathology beginning at approximately 3 months of age. Infrared microspectroscopy allows analysis of untreated, flash frozen tissue samples, at micron level spatial resolution, and was used in this study to examine creatine deposits in the Alzheimer’s diseased brain. Creatine is central to cellular energetics and plays an important role in proper brain function. The hippocampi of 7 pairs of transgenic mice and their littermate controls were mapped using infrared microspectroscopy and the results were analyzed for creatine levels and levels of β-sheet, indicative of the presence of β-amyloid plaques. Creatine was found to be focally elevated in the transgenic mice, as compared to their littermate controls but was not co-localized with β-amyloid plaques. Further surveys of serial sections from one transgenic mouse showed the 3-dimensional distribution of creatine within the sample. Focally elevated creatine may be a marker of the disease process, indicative of disturbed energy metabolism or inflammatory response to the disease progression.

No description available.

Alzheimer’s disease (AD) is the most reoccurring type of dementia, and remains incurable. Much work has been done to investigate the connections between AD development, type 2 diabetes and insulin receptor signaling abnormalities. Full length amyloid precursor protein (flAPP) is a large transmembrane protein that has significant physiological activities including in utero fetal development. Alpha secretase enzymes cleave flAPP, producing secreted amyloid precursor protein alpha (sAPPα), which has neuroprotective properties, including protection against neuronal apoptosis as well as the induction of neuronal outgrowth. There is no known dedicated receptor for the physiological action of sAPPα. Our data suggest that the physiological actions of sAPPα are a result of the physical interaction between sAPPα and the neuronal insulin receptor. We have shown that sAPPα phosphorylates, and thus activates, the neuronal insulin receptor as well as specific downstream proteins, including insulin receptor substrate (IRS), and protein kinase B (Akt). We have also shown that the observed interaction between sAPPα and neuronal insulin receptors is physical and that sAPPα competes with insulin for the insulin binding site. These findings may have implications for therapies aimed at slowing down the progression of AD through the activation of the insulin receptor pathway, since in neurons, insulin and the insulin receptor pathway are critical to the neuronal health and plasticity.

Infrared microspectroscopy has been used to survey Alzheimer’s diseased brain tissue from a transgenic mouse model of the disease. Alzheimer’s disease is the leading cause of dementia among the elderly and is characterized by β-amyloid plaque deposition,neurofibrillary tangles, inflammation, and disturbed energy metabolism in the brain. Both the TgCRND8 and Tg19959 mouse models of the disease develop Alzheimer’s disease pathology beginning at approximately 3 months of age. Infrared microspectroscopy allows analysis of untreated, flash frozen tissue samples, at micron level spatial resolution, and was used in this study to examine creatine deposits in the Alzheimer’s diseased brain. Creatine is central to cellular energetics and plays an important role in proper brain function. The hippocampi of 7 pairs of transgenic mice and their littermate controls were mapped using infrared microspectroscopy and the results were analyzed for creatine levels and levels of β-sheet, indicative of the presence of β-amyloid plaques. Creatine was found to be focally elevated in the transgenic mice, as compared to their littermate controls but was not co-localized with β-amyloid plaques. Further surveys of serial sections from one transgenic mouse showed the 3-dimensional distribution of creatine within the sample. Focally elevated creatine may be a marker of the disease process, indicative of disturbed energy metabolism or inflammatory response to the disease progression.