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Alzheimer's disease Synonyms and keywords:AD;Alzheimer's; Alzheimer dementia; Alzheimer disease; Alzheimer sclerosis; Alzheimer's syndrome; Alzheimer-type dementia; Presenile and senile dementia; Primary senile degenerative dementia; Senile dementia of the Alzheimer type; SDAT; Alzhiemer dementia; Alzhiemer's; Alzheimer's dementia care; Alzheimer's caregiving

Overview

Alzheimer's disease is the most common cause of dementia among older people. Dementia is a loss of thinking, remembering, and reasoning skills that interferes with a person's daily life and activities. Other causes of dementia include blood vessel disease in the brain (called vascular dementia), Parkinson's disease, frontotemporal dementia, and Lewy body dementia. The first case of Alzheimer's disease was described by a German psychiatrist named Alöis Alzheimer in the year 1901. For many decades after Alzheimer's original description, there was little progress in defining the pathogenesis of AD occurred. In the mid 1970's, it was found that the levels of acetylcholine decrease in brains of individuals undergoing neurodegeneration due to Alzheimer's disease. In early 1980's major advances in biochemistry and molecular genetics allowed the use of compositional analyses and immunocytochemistry to explain the structure of tangles and plaques found in the brains of Alzheimer patients. The term Alzheimer's disease was subsequently formally adopted in medical nomenclature to describe individuals of all ages with a characteristic common symptom pattern, disease course, and neuropathology. Alzheimer's disease may be classified according to severity into mild, moderate and severe dementia. It may also be classified based on age of onset into early onset and late onset Alzheimer's disease. Another method of classification of Alzheimer's disease is based on the course of disease into pre-dementia, early dementia, moderate dementia and advanced dementia. Alzheimer disease (AD), is a progressive neurodegenerative disorder. The dysfunction of amyloid precursor protien (APP) metabolism and the resulting build up of of Aβ peptides and their aggregation in the form of senile plaques in the brain parenchyma of individuals have been considered pivotal for neurodegeneration in the disease. Cognitive impairment in patients with AD is closely associated with synaptic loss in the neocortex and limbic system. The microscopic histopathological features of alzheimer's disease consist of neurofibrillary tangles, senile plaques, neuronal loss, and with or without cerebral amyloid angiopathy. Alzheimer's disease may be caused by trisomy of chromosome 21, familial inheritance of mutations in either presenilin 1 gene, presenilin 2 gene or APOE4 gene. Presenilin mutations are associated with early onset Alzheimer's disease, whereas APOE mutations are associated with late onset disease. Environmental factors, such as aging, low level of education and head trauma may also contribute to the development of Alzheimer's disease. An estimated 5.5 million Americans of all ages have Alzheimer's disease. An estimated 10,000 per 100,000 individuals aged greater than 65 years have been known to be living with Alzheimer's disease in the United States. The diagnosis of Alzheimer's disease (AD) is made on the basis of clinical criteria described by either the National Institute on Aging and the Alzheimer's Association (NIA-AA) or DSM-V (Diagnostic and Statistical Manual of Mental Disorders, fifth edition). Histopathologic examination for diagnosis of Alzheimer's disease is rarely done. Elderly patients presenting with progressive decline in memory and other cognitive impairments such as aphasia, agnosia or apraxia should be suspected for Alzheimer's disease. In these patients, mental status examination (MSE) and neuropsychological testing should be performed to further evaluate the status of cognitive abilities. Diagnostic tools for the examination of the patient include mini- mental status examination (MMSE), Montreal Cognitive Assesment (MOCA) and instruments of activities of dailing living (IADL). Characteristic findings on MRI suggestive of Alzheimer's disease include reduced hippocampal volume and medial temporal lobe atrophy. There is no known cure for Alzheimer's disease (AD). Available treatments offer relatively small symptomatic benefit but remain palliative in nature. Current treatments can be divided into pharmacological, psychosocial, and caregiving. Acetylcholine esterase inhibitors increase the amount of acetylcholine in the brain and are a major part of pharmacotherapy for Alzheimer's disease. Major drugs include, donepezil, rivastigmine and galantamine, these drugs help with the cognitive symptoms of the disease. Associated psychosis and depression may be managed with antipsychotics and selective serotonin reuptake inhibitors (SSRIs). Caregiving plays a pivotal role in the management of patients suffering from Alzheimer's disease.

Historical Perspective

• In 1901 when Alöis Alzheimer, a German psychiatrist, identified the first case of what became known as Alzheimer's disease in a fifty-year-old woman whom he referred to as Auguste D.
• Alöis Alzheimer followed her until she died in 1906, at which point he reported the case publicly for the first time
• In the following five years, eleven similar cases were reported in the medical literature, some of them already using the term Alzheimer's disease
• In 1910, Emil Kraepelin recognized Alzheimer's dementia as a separate entity in the eighth edition of his 'Textbook of Psychiatry', which was later published.
• For many decades after Alzheimer's original description, there was little progress in defining the pathogenesis of AD occurred. The diagnosis of Alzheimer's disease was reserved for individuals between the ages of 45 and 65 who developed symptoms of dementia
• In late 1960s, with the advent of electron microscopy, Michael Kidd in England and Robert Terry in the United States deciphered the microscopic changes underlying senile (neuritic) plaques and neurofibrillary tangles
• In the mid 1970's, it was found that the levels of acetylcholine decrease in brains of individuals undergoing neurodegeneration due to Alzheimer's disease. As a result, pharmacological therapy became more focused on increasing the levels of acetylcholine across the synaptic clefts of Alzheimer patients
• In the late 1970's and early 1980s, it was identified that the levels of neurotransmitters other than acetylcholine were also changed in affected patients
• In the late 1970's and early 1980s, it was identified that the levels of neurotransmitters other than acetylcholine were also changed in affected patients
• In early 1980's major advances in biochemistry and molecular genetics allowed the use of compositional analyses and immunocytochemistry to explain the structure of tangles and plaques. This eventually led to the use of Alzheimer's disease independently of the age of onset of the disease
• The term Alzheimer's disease was subsequently formally adopted in medical nomenclature to describe individuals of all ages with a characteristic common symptom pattern, disease course, and neuropathology

Classification

Classification based on severity

Alzheimer's disease may be classified based on the clinical dementia rating criteria into minimal, intermediate, mild, moderate and severe:

Clinical Dementia Rating
Based on severity of Impairment
Criteria	Minimal	Indeterminate	Mild	Moderate	Severe
Memory	No memory loss or slight forgetfulness	Minimal forgetfulness; partial recollection of events; “benign” forgetfulness	Moderate memory loss; more marked for recent events; defect interferes with everyday activities	Severe memory loss; only highly learned material retained; new material rapidly lost	Severe memory loss; only fragments remain
Orientation	Fully oriented	Fully oriented except for slight difficulty with time perception	Moderate difficulty with time perception; oriented for place at examination; may be disoriented to place	Severe difficulty with time relationships; usually disoriented to time, often to place	Oriented to person only
udgment and problem solving	Able to handle daily life activities (including financial issues); judgment good in relation to past performance	Mild impairment in solving problems, determining similarities and differences	Moderate difficulty in solving problems, difficulty in distinguishing things; social judgment usually maintained	Severely impaired in solving problems, determining similarities and differences; social judgment usually impaired	Unable to make judgments or solve problems
Social functioning	Functions independently and performs daily tasks such as shopping, and volunteer and social groups	Slight impairment in performing social activities	Unable to perform social activities, although may still be engaged in some; appears normal on casual observation	No pretense of independent function outside of home; appears well enough to be taken to functions outside a family home	No pretense of independent function outside of home; appears too ill to be taken to functions outside a family home
Home and hobbies	Able to carry out daily life activities, hobbies, and intellectual interests well maintained	Daily life tasks, hobbies, and intellect slightly impaired	Mild but definite impairment of function in performing daily life tasks; more difficult chores abandoned; more complicated hobbies and interests abandoned	Only simple chores preserved; interests very restricted and poorly maintained	No significant function in home
Personal care	Able to take care of self	Fully functional	Needs reminders	Requires assistance in dressing, hygiene, keeping of personal effects	Requires much help with personal care; frequent incontinence