Alzheimer's disease is the primary source of dementia in older individuals. That is, in people who are older than 60, more than 50% of all cases of dementia-which represents a progressive decline in cognition, emotion, and behavior-can be imputed to Alzheimer's disease.
Alzheimer's disease can be diagnosed definitively only after someone has died. That is, only a histo-pathological examination can identify the neuropathological features that characterize Alzheimer's disease.
Nevertheless, practitioners might confer a clinical diagnosis of probable Alzheimer's disease. The National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) stipulate the criteria that are most frequently applied to reach this diagnosis. First, individuals must demonstrate a progressive decline in cognitive, emotional, on behavioral functioning, beginning between the ages of 40 to 90. Second, they must exhibit an impairment in memory as well as a deficit in one other domain of cognition. Third, the dementia cannot be imputed to other causes, and consciousness should not be disturbed (McKhann, Drachman, Folstein, Katzman, Price, & Stadlan, E. M., 1984).
During the preliminary stages of Alzheimer's Disease, individuals often forget recent events. They might exhibit other cognitive impairments, such as difficulties with retrieving words and confusing with navigating around familiar environments.
These symptoms, however, do not depart appreciably from the usual signs of healthy aging. Indeed, during this stage, individuals can usually fulfill most of their daily activities, with negligible impairment.
As Alzheimer's Disease progresses, deficits extend to understanding of concepts and semantic memory. Furthermore, difficulties with movement and action can transpire. In addition, executive functioning, such as planning of actions, inhibiting responses, monitoring errors, and reaching decisions. As a consequence, individuals begin to demonstrate impairments in their capacity to fulfill their daily activities.
During the more advanced stages of Alzheimer's Disease, these impairments are more acute. Changes in mood and temperament are often apparent as well, including aggression and agitation. These impairments can escalate to limitations in locomotion, continence, and recognition of individuals.
During the preliminary phases, neuropsychological assessments often reveal deficits in episodic memory. That is, individuals cannot readily recall information that was presented recently, such as pairs of words. Indeed, this deficit often precedes the diagnosis of probable Alzheimer's Disease by a few years (Arnaiz & Almkvist, 2003;; Hodges, 2006;; Swainson, Hodges, Galton, Semple, Michael, Dunn, et al. 2001). Specifically, even during this stage, individuals cannot readily remember pairs of words or concepts that were presented earlier, referred to as a deficit in associative memory functions (Blackwell, Sahakian, Vesey, Semple, Robbins, & Hodges, 2004;; Fowler, Saling, Conway, Semple, & Louis, 2002). Memory deficits have been shown in visual, verbal, and olfactory domains.
Nevertheless, even during these stages, other cognitive deficits, particularly in semantics, attention, and executive function, are also frequently observed (Hodges, 2006). As Alzheimer's Disease progresses, other cognitive deficiencies, including visuospatial, perceptual, and language, impairments become apparent (Hodges, 2006).
In addition to cognitive deficits, emotional problems can emerge, such as apathy, depression, and-although less frequent-agitation and aggression (Aarsland, Cummings, & Larsen, 2001;; Lyketsos, Lopez, Jones, Fitzpatrick, Breitner, & DeKosky, 2002). Furthermore, awareness or insight into deficits may also deteriorate as Alzheimer's Disease progresses, although methodological variations have obscured the clarify of this issue (Markova & Berrios, 2006).
Olfaction often declines in older individuals. Nevertheless, the decline in Alzheimer's Disease is more conspicuous (Nordin & Murphy, 1998) and has been established in many studies (e.g., Doty, Reyes, & Gregor, 1987;; Koss, Weiffenbach, Haxby, & Friedland, 1987;; Mesholam, Moberg, Mahr, & Doty, 1998;; Peabody & Tinklenberg, 1985;; Rezek, 1987;; Warner, Peabody, Flattery, & Tinklenberg, 1986).
Olfactory thresholds-that is, the capacity to detect an odor-might be deficient in Alzheimer's Disease (e.g., Chan, Tam, Murphy, Chiu, & Lam, 2002;; Murphy, Gilmore, Seery, Salmon, & Lasker, 1990). Furthermore, individuals with Alzheimer's Disease often rate odors as less intense than do their healthy counterparts (Royet, Croisile, Williamson-Vasta, Hibert, Serclerat, & Guerin, 2001). Nevertheless, some studies have observed no differences in olfactory thresholds between individuals with or without Alzheimer's Disease (e.g., Koss, Weiffenbach, Haxby, & Friedland, 1988).
According to Murphy, Gilmore, Seery, Salmon, and Lasker (1990), differences between these sets of studies might reflect variations in the severity of Alzheimer's Disease across samples. Detection thresholds might rise only when Alzheimer's Disease has progressed considerably, as reflected by the Mini-Mental State Examination or Dementia Rating Scale.
Similarly, whether odor discrimination is impaired in patients with Alzheimer's Disease has not been established definitively. Some studies show that discrimination-that is, the capacity to ascertain whether or not two odors are different-is impaired in Alzheimer's Disease (e.g., Knupfer & Spiegel, 1986). Other studies have not uncovered any impairment (Hughes, Struble, & Shaffer, 2001).
In contrast to detection and discrimination, deficits in olfactory identification in Alzheimer's Disease have been found consistently across studies (Peabody & Tinklenberg, 1985), even in the early stages of this disease. That is, these patients cannot readily determine which of several alternatives correspond to the odor they just smelled. This finding applies regardless of whether the alternatives are presented as verbal labels (Kareken, Doty, Moberg, Mosnik, Chen, Farlow et al., 2001;; Kjelvik, Sando, Aasly, Engedal, & White, 2007;; Morgan & Murphy, 2002), or pictures (Chan, Tam, Murphy, Chiu, & Lam, 2002;; Morgan & Murphy, 2002). Olfactory memory is also impaired in individuals with Alzheimer's Disease (Gilbert, Barr, & Murphy, 2004). Again, this finding seems to be universal rather than contentious.
Semantic memory, as measured by tasks such as fluency in naming instances of some category, seems to be deficient in patients with Alzheimer's Disease. Initially, these findings were ascribed to difficulties with retrieving or accessing semantic knowledge. For example, these differences had been shown to dissipate when implicit tasks were used to assess semantic memory (e.g., Nebes, 1989). More recent studies, however, seem to imply that semantic information might actually be lost in Alzheimer's Disease, at least partially (e.g., Garrard, Lambon Ralph, Patterson, Pratt, & Hodges, 2005), but is exacerbated by difficulties in retrieval. Subtle deficits in semantic memory can even be detected during the early stages of this disease (Vogel, Gade, Stokholm, & Waldemar, 2005).
The neuropathology of Alzheimer's Disease is characterised by two key indices: an accumulation of neurofibrillary tangles (NFTs) in the intracellular cytoplasm, and beta-amyloid plaques in the extracellular space. Neurofibrillary tangles appear within neurons and comprise hyper-phosphorylated tau protein-a protein that is needed to stabilize the microtubule system that underpins intracellular transport. Extra phosphate groups combine with the tau protein. In response, this tau protein forms pairs of helical filaments called neurofibrillary tangles.
Beta-amyloid plaques, in contrast, represent a consolidation of amino acid peptide fragments, called beta-amyloid. In particular, a progressive and incessant imbalance between the production and elimination of these amino acid peptide fragments culminates in amyloid plaques. These accumulation of these beta-amyloid plaques provokes neurodegeneration and dementia (Christensen, 2007;; Masters & Beyreuther, 2006).
The distribution of neurofibrillary tangles and beta-amyloid plaques differ from each other. Neurofibrillary tangles first appear in the transentorhinal area within the medial temporal lobes and are later observed in the entorhinal cortex, the hippocampus, and other limbic structures before reaching the neocortex (Braak & Braak, 1991, 1995). In contrast, beta-amyloid plaques first appear in the neocortex and are later observed in the hippocampus, the entorhinal cortex, as well as the insular cortex, and eventually the striatum, basal forebrain, and several brainstem nuclei.
As the neurofibrillary tangles accumulate, cognitive deficits are more likely to manifest (e.g., Bennett, Schneider, Wilson, Bienias, & Arnold, 2004;; Giannakopoulos, Herrmann, Bussiere, Bouras, Kovari, Perl, et al., 2003). Giannakopoulos, Herrmann, Bussiere, Bouras, Kovari, Perl, et al. (2003), however, report no relationship between the accumulation of beta-amyloid plaques and cognitive functioning. Bartoo, Nochlin, Chang, Kim, and Sumi (1997), in contrast, did uncover such a relationship.
Conceivably, to reconcile these findings, beta-amyloid plaques, which appear early in the disease, accelerate the formation of neurofibrillary tangles. However, the neurofibrillary tangles, not the beta-amyloid plaques, may be responsible for the cognitive deficits.
Until recently, both neurofibrillary tangles and beta-amyloid plaques could be assessed only post mortem. In the last few years, however, PET radiotracers specific to beta-amyloid have been developed and utilized to establish the possible presence of these deposits while the participant is alive. The tracer that has been validated most extensively,
known commercially as Pittsburgh Compound B (Klunk, Engler, Nordberg, Wang, Blomqvist, Holt, et al, 2004), is a derivative of the thioflavin-T amyloid dye and binds specifically to beta-amyloid plaques (Mathis et al., 2002).
Several studies have validated Pittsburgh Compound B. For example, PET studies have shown a relationship between Pittsburgh Compound B binding and rate of cerebral atrophy in Alzheimer's Disease (Archer, Edison, Brooks, Barnes, Frost, Yeatman, et al., 2006) and with limited metabolism of the temporo-parietal cortex (Edison, Archer, Hinz, Hammers, Pavese, Tai, et al., 2007).
MRI studies, especially when focused on targeted regions of interest, have shown the volume of several structures in the medial temporal lobe is reduced, even in the early stages. These structures include the entorhinal cortex, the perirhinal cortiex, and the hippocampus (Bobinski et al., 1999;; Convit et al., 1993;; de Leon et al., 1996;; Du et al., 2001)-the regions in which neurofibrillary tangles first accumulate. Such losses in volume do indeed correlation with memory impairment in Alzheimer's Disease (Chetelat, Desgranges, de la Sayette, Viader, Berkouk, Landeau, et al., 2003). In addition, other regions have also demonstrated some volumetric loss in the early stages, including
the precuneus and the posterior cingulate gyrus (Fox, Crum, Scahill, Stevens, Janssen, & Rossor, 2001;; Scahill, Schott, Stevens, Rossor, & Fox, 2002).
Several risk factors of Alzheimer's Disease have been identified. First, age is perhaps the primary risk factor. The prevalence of Alzheimer's Disease is approximately 1% for individuals aged between 60 to 65, 6 to 10% for individuals aged between 65 to 85, and 25% for individuals aged over 85 (Hendrie, 1998;; Yesavage, O'Hara, Kraemer, Noda, Taylor, Ferris, et al., 2002).
Because of the population of industrial countries tends to be aging, the global burden of dementia is anticipated to rise exponentially over the next 10 to 20 years. Approximately, 4.5 million additional cases of Alzheimer's Disease are diagnosed every year (Ferri, Prince, Brayne, Brodaty, Fratiglioni, Ganguli, et al., 2005).
Second, family history of Alzheimer's Disease is perhaps the next most significant risk factor. Third, older individuals who experience depression and apathy and also demonstrate mild cognitive impairment are especially likely to progress to Alzheimer's Disease at a more rapid rate (Apostolova & Cummings, 2008;; Teng, Lu, & Cummings, 2007).
Many studies indicate that depression may increase the likelihood of subsequent Alzheimer's Disease (for a review, see Namekawa, Y. et al., 2013). When depression first appears while individuals are young, the likelihood of developing Alzheimer's Disease increases by 3.8.
Conceivably, the formation of B amyloid plaques underpins the association between depression and Alzheimer's Disease. To illustrate, Namekawa, Y. et al. (2013) found the ratio of serum B amyloid 40 and B amyloid 42 was higher in patients with depression than healthy control participants, especially if the depression was first experienced when young. In addition, serum B amyloid 42 was lower in depressed patients. These findings imply that depression may affect the metabolism of B amyloid, ultimately contributing to Alzheimer's Disease.
During the mild to moderate stages of Alzheimer's Disease, a collection of drugs, called acetylcholinesterase inhibitors, are sometimes administered to delay the progression of symptoms by approximately 6 to 12 months. Many scholars contend that acetylcholinesterase inhibitors do alleviate symptoms, although some controversies over these benefits still abound (for reviews and debates, see Ames, Kaduszkiewicz, van den Bussche, Zimmermann, Birks, & Ashby, 2008;; Ashby, 2008;; Birks, 2008;; Kaduszkiewicz, van den Bussche, & Zimmermann, 2008).
Other drugs have been administered to individuals during the moderate to severe stages of Alzheimer's Disease. Memantine, a glutamate NMDA antagonist, has been shown marginally improve the cognitive performance of these individuals (McShane, Areosa Sastre, & Minakaran, 2006).
Rather than alleviate symptoms, some recent pharmacological approaches, designed to redress the pathogenesis of Alzheimer's Disease, have been examined. In particular, these clinical trials have examined the efficacy of immunotherapies, secretase inhibitors, selective A?42-lowering agents, statins, and anti-A? aggregation agents (Christensen, 2007;; Masters & Beyreuther, 2006). Giacobini and Becker (2007) predict some of these approaches might be available within 5 to 10 years of their article.
Cognitive stimulation therapy has been shown to improve mental functioning, cognition, and quality of life in people with dementia, including Alzheimer's Disease. In the study conducted by Spector, Thorgrimsen, Woods, Royan, Davies, Butterworth, and Orrell (2003), participants were exposed to a program that comprises 14 sessions, each spanning 45 minutes, over seven weeks. During these sessions, the individuals participated in tasks that involve solving word puzzles, using money, and famous faces. Furthermore, to instill a sense of continuity, a board was displayed, presenting personal information as well as other details to clarify the context. In addition, each session began with a softball game, also to ensure consistency and familiarity.
The tasks were designed to foster information processing rather than merely the retrieval of factual knowledge. For example, after participants observed a series of faces, they were asked to identify which person appears to be the youngest and to uncover a feature they share in common. This program improved functioning, as measured by the mini mental state examination and a measure of quality of life.
In reminiscence therapy, participants are invited to reflect upon various facets of their lives in the past--perhaps a specific time or domain. Photographs, music, documents, and other stimuli are used to stimulate discussion. Okumura, Tanimukai, and Asada (2008), for example, examined the benefits of this intervention. Five sessions of reminiscence therapy were conducted. In the control group, researchers merely engaged in typical conversations, but did not discuss the previous life history of participants. Word recall improved after these five sessions of reminiscence therapy.
Often, to remember a set of items, people will learn or listen to a song in which the material to be memorized is embedded, called music mnemonics. Simmons-Sterna, Budsona, and Allya (2010) showed that music mnemonics are especially likely to enhance the memory of people with Alzheimer's disease. In this study, the participants listened to the lyrics of an unfamiliar song. In one condition, the lyrics were sung. In the other condition, the lyrics were not sung. The singing improved recognition memory in people with Alzheimer's disease but not in healthy older adults. Music may amplify arousal and, thus, improve memory. Alternatively, brain regions that underpin the processing of music may be intact in people with Alzheimer's disease.
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Last Update: 6/19/2016