**Early Detection of Alzheimer's Disease with Cognitive Neuroscience Methods**

Jinglong Wu, Chunlin Li and Jiajia Yang

*Biomedical Engineering Laboratory, Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan* 

#### **1. Introduction**

36 Neuroimaging for Clinicians – Combining Research and Practice

Zhang Y, Schuff N, Du AT, et al. White matter damage in frontotemporal dementia

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and Alzheimer's disease measured by diffusion MRI. Brain 2009;132:2579–

Recently, the exploration of human brain function was examined in cognitive neuroscience and brain science. Along with the development of engineering technology, such as measurement technology, information technology, and artificial intelligence, we can record the brain activity on the timeframe of milliseconds or at the level of a single neuron to examine basic visual function or high level brain function (e.g., memory, language, or attention). In this chapter, we introduce a new research field that combines engineering and cognitive neuroscience, which was named "Neuromedical Engineering". We focused our research on five topics: 1. tactile perception and neurology (Yang et al., 2011a, 2011b, 2011c, 2010a, 2011; Wu et al., 2010a, 2011); 2. attention and cognitive brain function (Wu & Li, 2009) and multisensory integration (Li et al, 2009a, 2010a, 2010b; Touge et al., 2008; Wu & Kakura, 2010; Wu et al., 2009); 3. basic visual cognition (Li et al., 2009b; Wu et al., 2011; Yan et al., 2011); 4. language (Cai et al., 2007; Li et al., 2011a, 2011b; Wu et al., 2007); and 5. tactile perception and rehabilitation (Bai et al., 2010). Focusing on these five topics, we provide information on human brain function and neurology. Furthermore, using these cognitive and neurological methods, we are challenging the topic of "Early Detection of Alzheimer's Disease with Cognitive Neuroscience Methods".

The earliest symptoms of Alzheimer's disease (AD) involves learning, memory or planning problems. Currently, no medical tests are available to diagnose AD conclusively premortem. However, several studies have used cognitive tasks (i.e., visuospatial tasks and language tasks) to discover preclinical cognitive markers of AD. These studies demonstrated that the cognitive deficits of AD can possibly be detected during a preclinical period that spans several years. In addition, numerous neuropathological, electrophysiological and neuroimaging studies support the hypothesis that cognitive deficits in AD are related to a possible disconnection between cortical areas. In this chapter, we describe current studies and possible future experiments on the early diagnosis method using cognitive and functional imaging testing to help with the clinical diagnosis of AD.

People with AD die an average of four to six years after diagnosis, but the duration of the disease can vary from three to 20 years. As shown in Fig. 1, the rate of cognitive decline in patients with AD was faster than healthy subjects after a specific point (before diagnosis). This specific point may be detectable using memory and planning tasks, such as visuospatial and language tasks. Recent studies have demonstrated that the cognitive deficits of AD can be detected using some simplex cognitive tests.

Early Detection of Alzheimer's Disease with Cognitive Neuroscience Methods 39

free recall of rapidly presented random words, free recall of slowly presented random words, free recall of organisable words and cued recall of organisable words. The key finding from this study suggested that although the non-dementia subjects slightly declined across the three year retest interval, the incident AD subjects showed a significant performance deficit at baseline, which was further exacerbated long-term. These findings suggest that the time of AD diagnosis is characterised by a significant decline of episodic memory. In addition, this study also indicated that a combination of global and specific cognitive measures may optimise the identification of individuals in a preclinical phase

In addition, numerous neuropathological and neuroimaging studies have suggested that the cognitive deficits in AD were related to a possible disconnection between cortical areas. The tactile and visual objects cognition are the major manual learning and memory skills of humans, which also require extensive connections between cortical areas. Thus, preclinical alterations in AD are not restricted to language tasks. There are many studies that have attempted to find cognitive markers of AD using visual, auditory or tactile tasks. This review suggested that the preclinical cognitive deficit markers of incident AD may be

In this chapter, we first introduce a normal study on visual and auditory orienting attention using functional magnetic resonance imaging (fMRI). Secondly, a unique tactile angle discrimination experiment was introduced, which found significant behavioural cognitive

**2. Pilot fMRI study on spatial and temporal attention cognition of normal,** 

The human brain is a highly efficient information processing system capable of handling a large amount of information rapidly and simultaneously. If we were able to elucidate the sophisticated mechanisms of the brain accurately, we could construct flexible, efficient, humanlike artificial systems. We would also have the capacity to assess the most relevant

Previously, we studied the human visual and auditory systems, which convey almost all external information, with an emphasis on the parallel processing of visual and auditory data. In human information processing systems, attention plays an important role in selecting and integrating information. Previous studies on attention have proposed various psychological models, which are supported by a variety of psychological and physiological evidence. The neuronal substrate of the human attention system has also been investigated using positron emission tomography (PET) and fMRI to examine visual and auditory attention in humans using audiovisual stimuli. However, the common and unique networks used by the visual and auditory attention systems remains poorly understood. Furthermore, attention to time has not been studied sufficiently compared to space, and little research has compared the differences between the visual and auditory systems regarding spatial and

In this study, we analysed spatial and temporal attention using both visual and auditory stimuli. To evaluate these processes behaviourally, we conducted psychological experiments where we measured the reaction times (RTs) for each task. To reveal the neuronal networks

related to these attention systems, we measured the haemodynamics using fMRI.

detectable using a combination of multisensory cognitive or functional MRI tasks.

differences between normal aging and dementia.

ways to present information and in the most appropriate manner.

of AD.

**young subjects 2.1 Introduction** 

temporal attention.

Previous studies have suggested that both amyloid plaques and neurofibrillary tangles are clearly visible in AD brains using microscopy. The plaques and tangles spread through the cortex in a predictable pattern as AD progresses (Fig. 2). First, during the earliest AD stage, the atrophy of brain cortices occurs in the hippocampus and the surrounding areas, and the changes may begin 20 years or more before diagnosis. Second, during the mild to moderate stages, the damage to the brain cortices is found in the temporal and parietal lobes and parts of the frontal cortex and cingulate gyrus. Finally, during the advanced AD stage, the degeneration of atrophy is found in the whole brain.

Fig. 1. The change of cognitive function deficiency model of aging healthy individuals and patients with AD.

Because the damage to the brain cortices occurs in the hippocampus, the early symptoms are mild memory loss. The first symptoms are often mistaken as related to aging or stress, but these early cognitive deficits can also be symptomatic of the early stages of AD and detected using long-term cognitive tests.

Fig. 2. The damaged cortex areas of AD patients during different stages.

Several studies have attempted to identify the preclinical cognitive markers of AD. Bäckman and Small (2007) used four episodic memory tasks on old non-dementia and incident AD subjects to investigate the cognitive deficit changes over three years. These tasks consisted of free recall of rapidly presented random words, free recall of slowly presented random words, free recall of organisable words and cued recall of organisable words. The key finding from this study suggested that although the non-dementia subjects slightly declined across the three year retest interval, the incident AD subjects showed a significant performance deficit at baseline, which was further exacerbated long-term. These findings suggest that the time of AD diagnosis is characterised by a significant decline of episodic memory. In addition, this study also indicated that a combination of global and specific cognitive measures may optimise the identification of individuals in a preclinical phase of AD.

In addition, numerous neuropathological and neuroimaging studies have suggested that the cognitive deficits in AD were related to a possible disconnection between cortical areas. The tactile and visual objects cognition are the major manual learning and memory skills of humans, which also require extensive connections between cortical areas. Thus, preclinical alterations in AD are not restricted to language tasks. There are many studies that have attempted to find cognitive markers of AD using visual, auditory or tactile tasks. This review suggested that the preclinical cognitive deficit markers of incident AD may be detectable using a combination of multisensory cognitive or functional MRI tasks.

In this chapter, we first introduce a normal study on visual and auditory orienting attention using functional magnetic resonance imaging (fMRI). Secondly, a unique tactile angle discrimination experiment was introduced, which found significant behavioural cognitive differences between normal aging and dementia.
