Journal of Alzheimer's disease : JAD
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Death with dementia is increasingly common. Although prognostication is difficult, it is an incurable life-limiting illness for which palliative care for the patient is often appropriate. Dementia patients are otherwise at risk of overtreatment with burdensome and possibly non-beneficial interventions and undertreatment of symptoms. ⋯ Guidelines for care and treatment, still mostly consensus-based, support the benefits of advance care planning, continuity of care, and family and practitioner education. Assessment tools for pain, prognosis, and family evaluations of care have been developed and some have been shown to be effective in clinical practice. With increasing numbers of well-designed, large-scale studies, research in the next decade may result in better evidence-based guidelines and practice.
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We first proposed the mitochondrial cascade hypothesis of sporadic Alzheimer's disease (AD) in 2004. Our core assumptions were a person's genes determine baseline mitochondrial function and durability, this durability determines how mitochondria change with advancing age, and critical changes in mitochondrial function initiate other pathologies characteristic of AD. Since then several lines of investigation report data consistent with or supportive of our hypothesis. ⋯ As predicted, AD therapies designed to reduce Abeta thus far have had at best very limited clinical benefits; our hypothesis identifies alternative therapeutic targets. While placing mitochondria at the apex of an AD cascade certainly remains controversial, it is increasingly accepted by the AD research community that mitochondria play an important role in the late-onset forms of the disease. Even if the mitochondrial cascade hypothesis proves incorrect, considering its assumptions could potentially advance our understanding of sporadic, late-onset AD.
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Increasing evidence indicates that patients develop post-operative cognitive decline (POCD) following surgery. POCD is characterized by transient short-term decline in cognitive ability evident in the early post-operative period. This initial decline might be associated with increased risk of a delayed cognitive decline associated with dementia 3 to 5 years post-surgery. ⋯ Inflammation and a maladaptive stress response might also contribute to the pathophysiology of this disorder. Future research needs to identify predisposing factors, and then strategies to protect against POCD and subsequent dementia. The field also needs to adopt a more rigorous approach to codifying the frequency and extent of early and delayed post-operative cognitive decline.
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Recent studies have suggested that general anesthesia may initiate or accelerate cognitive impairment and Alzheimer's disease (AD). To understand the possible underlying mechanisms, several studies have been carried out in animal models. In this review, we first briefly discuss the mechanisms leading to neurodegeneration and cognitive impairment in AD, with an emphasis on tau abnormalities in this pathological process. ⋯ Recent studies suggest that anesthesia may accelerate the development of AD by promoting abnormal hyperphosphorylation of tau. Further studies are certainly needed to understand the molecular mechanism by which anesthesia may initiate or accelerate cognitive impairment and AD. An understanding of the mechanism will help develop strategies for preventing or eliminating this adverse effect of anesthesia.
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The evaluation and management of patients with cognitive decline pose many diagnostic and therapeutic challenges. While most cognitive disorders need a standard screening for common reversible causes, the diagnosis of `not so usual' causes are delayed and often missed. ⋯ Many more metabolic, nutritional, endocrinal, toxic, post operative, autoimmune, cerebrovascular, genetic, infectious, and hemorheological factors are now emerging as unusual causes. This review deals with the recognition and evaluation of these unusual causes of cognitive decline.