History

Fact Explanation
History of old age and positive family history Alzheimer disease (AD) is genetically heterogeneous disease. Early onset familial Alzheimer disease is inherited in an autosomal dominant manner. AD is common among elderly population and the prevalence of AD increases with age. Approximately 10% of persons over age 70 years have significant memory loss and more than half of these individuals have AD. However early onset familial Alzheimer disease starts at the age of <60-65 years where the late-onset familial Alzheimer disease begins at age of >60-65 years.[1].
History of Down syndrome (DS) Usually all the patients with DS develops neuropathologic hallmarks of AD after age 40 years. It is suggested that lifelong over expression of APP on chromosome 21 encoding the amyloid precursor protein, leading to overproduction of β-amyloid in the brains of persons who have DS. This ultimately resulting AD. In persons with DS, amyloid-β (Aβ) deposition in the brain may begin in the first decade of life.[1].
Dementia Alzheimer disease (AD) is characterized by dementia.It is typically begins with subtle, thereby poorly recognized initially.But later on memory impairment slowly become more severe and ultimately leads to incapacitating.[1]. According to "amyloid cascade hypothesis" accumulation of amyloid-β (Aβ) peptide leads to pathogenesis of AD. It leads to formation of amyloid plaques and trigger tau hyperphosphorylations and the formation of neurofibrillary tangles (NFT). This process is finally leading to synaptic dysfunction, neuronal loss degeneration, and dementia. [2].
History of head trauma and hypertension History of head trauma and hypertension act as risk factors for development of AD.[5]. Even though no environmental agents have been proven to be directly involved in the pathogenesis of AD, head trauma can be leads to non-familial AD with a combination of other risk factors.[1].
Poor judgment Poor judgment refers to the inability to make appropriate decisions, a typical presentation of AD.[1],[3].
Language impairment Language impairment in AD is primarily a result of decline in semantic and pragmatic levels of language processing.Semantic processing contains language content including the words and their meaning difficulties with word finding, naming, and word comprehension. It also leads to semantic paraphasia, that means choosing incorrect words. Other findings include inventing words, loss of verbal fluency and also empty speech (using ambiguous referents). Pragmatic processing in AD leads to speaking too much at inappropriate times, digressing from the topic,talking too loudly and repeating ideas.All those features can found in AD.Some People with AD may also present with aphasia.[4].
Short term memory loss Significant impairment of short term memory can be seen. One of the outstanding clinical feature on presentation in most individuals with AD is inability to retain new information.Characteristic findings of short-term memory loss include, repetition of questions or statements,difficulty remembering the names of familiar people and also, frequently misplacing items. Working memory, long-term declarative memory, and implicit memory are affected in a lesser degree than short-term memory .[5].
Impairment of planning and organizational skills Patients with early stage of Alzheimer's disease may also present with difficulties with executive functions such as planning and organizational skills.[5].
Impaired judgment and problem solving skills Impairment of judgment and problem solving, and handling complicated tasks is a manifestation of mild cognitive impairment in early stage of AD. In moderate to severe form of disease,executive functions and logical reasoning found to be significantly deteriorated.[5].
Problems with driving Spatial disorientation in AD frequently causes problems with driving because individuals are less capable of estimating time and speed. So that individuals with mild AD also have to be carefully assessed for driving ability. [5].
Personality and behavioral changes Seen even at the mild cognitive impairment stage.That includes apathy, withdrawal, passivity, and reduced motivation. It is seen among 25%–50% of the cases with AD.[5].
Depression and mood changes Significant depressive symptoms and mood changes are reported in 20%–30% of cases with early-stage AD. However the features like Agitation,anxiety ,and psychosis are not typically seen in early stage of AD but may become more common with severe stage of the disease.[5].
Anosognosia That means unawareness of illness, that can be seen in 50% of individuals with AD. In many of those cases, this represents a domain-specific deficit in self-monitoring and should not be attributed to psychological denial.[5].
Difficulty retaining new information Commonly seen among patients with moderate to severe AD. They rapidly loss the newly learn things or may a fragment will be remain.So that the family members often described them as "living in the past".[5].
Disorientation One of the manifestation of moderate to severe form of disease. It becomes more pronounced and may occur even in familiar environments. Sometimes they may be unable to recognize family members or close relatives.[5].
Hallucinations Commonly seen in advanced stage of AD. Visual hallucination is the common form.[5].
Delusions and illusions Both are seen in advanced stage of the disease. Those common form of delusions include "theft” of misplaced items or “infidelity” of spouse.Illusionary misidentification also been reported.[5].
Agitation and aggression Agitation with temper tantrums, verbal or physical aggression can be seen in individuals with late stage of disease.[5].
Sleep disturbance Disruption of sleep–wake cycles can be found in late stage of disease.[5].Sleep disturbances in AD are believed to be a result of a progressive deterioration and decrease in the number of neurons in the suprachiasmatic nucleus.It causes fluctuations in neurohormones that are critical in the homeostatic maintenance of the circadian rhythm. That causes increased sleep latency, decreased slow-wave sleep, increased daytime napping and also causes nighttime sleep fragmentation.[6].
Sundowning It is another common manifestation occurring during the middle to late stages of AD. It is marked by an increase in confusion, wandering, and agitation that often (although not always) occurs in the late afternoon into the evening. And improvements seen during the daylight hours. Even though the nature of sundowning has been uncertain, it is believed to be related to a disturbance in circadian rhythm that lead in to significant delays in peak body temperature and alterations in endogenous melatonin secretion.[6].
Anxiety, and aimless Anxiety, and aimless or restless activities such as wandering or hoarding are common at late stage of the disease.[5].
Impaired chewing and swallowing In late stage of the disease,even basic motor functions such as chewing and swallowing can be impaired.They may required assistance with simple functions such as eating.[5].
Death due to complications Most patients became bedridden at the late stage of disease, and die due to complications such as aspiration, infection, or inanition.[5]. Death may also results from malnutrition, and pneumonia. The typical clinical duration of the disease is eight to ten years. But can range from one to 25 years.[1].
Confusion It is another recognized presentation of AD.[1].
References
  1. BIRD TD, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Alzheimer Disease Overview [online] 1993 [viewed 11 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301340
  2. WATTAMWAR PR, MATHURANATH PS. An overview of biomarkers in Alzheimer's disease Ann Indian Acad Neurol [online] 2010 Dec, 13(Suppl2):S116-S123 [viewed 11 September 2014] Available from: doi:10.4103/0972-2327.74256
  3. GALTON C. J.. Atypical and typical presentations of Alzheimer's disease: a clinical, neuropsychological, neuroimaging and pathological study of 13 cases. [online] 2000 March, 123(3):484-498 [viewed 11 September 2014] Available from: doi:10.1093/brain/123.3.484
  4. FERRIS SH, FARLOW M. Language impairment in Alzheimer's disease and benefits of acetylcholinesterase inhibitors Clin Interv Aging [online] 2013:1007-1014 [viewed 11 September 2014] Available from: doi:10.2147/CIA.S39959
  5. TARAWNEH R, HOLTZMAN DM. The Clinical Problem of Symptomatic Alzheimer Disease and Mild Cognitive Impairment Cold Spring Harb Perspect Med [online] 2012 May, 2(5):a006148 [viewed 11 September 2014] Available from: doi:10.1101/cshperspect.a006148
  6. DESCHENES CL, MCCURRY SM. Current Treatments for Sleep Disturbances in Individuals With Dementia Curr Psychiatry Rep [online] 2009 Feb, 11(1):20-26 [viewed 11 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2649672

Examination

Fact Explanation
Extrapyramidal signs Usually the general physical and neurological exam may remain normal throughout most of the course of AD. However Extrapyramidal signs are seen among 30% of people. Those exrapyramidal signs include, bradykinesia, rigidity, and reduced facial expression but resting tremor is a rare presentation.[1].
Gait disturbances It becomes more prominent with disease progression.and found to be associated with a substantially higher risk for falls.[1].
Primitive reflexes Present in some affected individuals. Those Primitive reflexes include snout and grasp reactions.[1].
Myoclonus Only a small proportion of individuals with severe AD experience myoclonus. But the incidence in of myoclonus in AD is higher than that in the general population.[1].
Epileptic seizures Found in a small proportion of patients who are suffering from severe Alzheimer's disease. But the incidence is found to be higher among AD than the normal population.[1].
Urinary incontinence Occasionally seen among affected individuals.[2].Double incontinence is common and most patients are bedridden at this stage.[1].
Impairment of episodic memory Cognitive assessment will show impairment of episodic memory including inability to learn and retain new information.Use of episodic memory testing is valuable in diagnosing patients with MCI (Mild cognitive impairment) who are likely to develop AD in near future. The tests usually assess immediate and delayed recall. There they asked to pay attention in certain tasks and assess their to immediate recall. Later on same thing is use for delayed recall. Few of thoses types of tests are free and Cued Selective Reminding Test, the Rey Auditory Verbal Learning Test, and the California Verbal Learning Test.[3].
Impaired executive functions Executive functions include set-shifting, reasoning, problem solving and planning ect. "Trail Making Test" is used to assess executive functions. Those are found to be impaired in cognitive assessment.[3].
Impairment of language skills In cognitive assessment language can be assessed by Boston Naming Test and letter and category fluency. Patients will show significant impairment in naming, fluency, expressive speech, and also comprehension.[3].
Impaired visuospatial skills A wide variety of clinical measures are available for the evaluation of cognitive and behavioral performance of people who suspected to have dementia. It is useful for diagnosis as well as follow up.[1]. Visuospatial skills can be assessed by "figure copying" method and found to be impaired in most individuals.[3].
Reduced attention Both simple and divided attention control can be assess by cognitive testing." Digit span forward" is used for that. most patients found to have impaired attention as well.[3].
References
  1. TARAWNEH R, HOLTZMAN DM. The Clinical Problem of Symptomatic Alzheimer Disease and Mild Cognitive Impairment Cold Spring Harb Perspect Med [online] 2012 May, 2(5):a006148 [viewed 12 September 2014] Available from: doi:10.1101/cshperspect.a006148
  2. BIRD TD, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Alzheimer Disease Overview [online] 1993 [viewed 11 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301340
  3. ALBERT MS, DEKOSKY ST, DICKSON D, DUBOIS B, FELDMAN HH, FOX NC, GAMST A, HOLTZMAN DM, JAGUST WJ, PETERSEN RC, SNYDER PJ, CARRILLO MC, THIES B, PHELPS CH. The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease Alzheimers Dement [online] 2011 May, 7(3):270-279 [viewed 12 September 2014] Available from: doi:10.1016/j.jalz.2011.03.008

Differential Diagnoses

Fact Explanation
Vascular Dementia Vascular dementia (VaD) is a heterogeneous phenotype that may result from a large spectrum of underlying vascular pathologies. Those include vascular brain injury, regional distribution of infarcts and hemorrhage.Information processing speed, working memory.abstraction and mental flexibility found to be affected. But verbal memory,specially retention was found to be preserved.[1].
Dementia with Lewy Bodies DLB is considered the second most common cause of dementia after AD. Other than dementia they may have recurrent well-formed visual hallucinations (42%), spontaneous parkinsonism (55%), and cognitive fluctuations (15%–85%). They are called core features and they usually apparent even dementia is mild. Other features include rapid eye movement (REM) sleep behavior disorder or neuroleptic sensitivity .They may also present with repeated falls and syncope, transient (unexplained) loss of consciousness, autonomic dysfunction, depression, systematized delusions, and hallucinations in other modalities.[1].
Alcohol-related dementia Excessive and prolonged use of alcohol may lead to permanent structural and functional damage. Chronic alcoholism may leads to alcohol related dementia (ARD) and alcohol induced persisting amnestic syndrome that also known as Wernicke-Korsakoff syndrome. Alcohol leads to direct neurotoxic effect as well as thiamine deficiency. Other than dementia alcohol may resulted in acute and chronic effects on cognitive function.Direct intoxication impairs most cognitive skills and in excess may lead to stupor and respiratory depression. Acute withdrawal in long-term alcohol abusers can result in tremor, hallucinations, seizures, agitation, and fluctuating levels of alertness.[2].
Frontotemporal Lobar Degeneration (FTLD) It is a heterogeneous group of disorders characterized by progressive neurodegeneration in the frontal and anterior temporal regions. It is commonly developed at the age of 45 to 65 yeas. It accounts about 20% of all patients with degenerative dementias.Some may also have positive family history. FTLD has 3 main subtypes. They are frontotemporal dementia (FTD), semantic dementia, and nonfluent aphasia. from them, FTD is predominant involved the right frontal lobe and leads to progressive behavioral and personality changes that disturb social conduct. Features include disinhibition, apathy, emotional blunting, lack of insight, disordered eating patterns, and executive dysfunction.Nonfluent aphasia have selective involvement of the left frontoinsular region. They may present with hesitant nonfluent speech, agrammatism, phonological errors, and speech apraxia. And the other form called semantic dementia predominantly involves the anterior temporal lobe. They can present with profound anomia and impaired word comprehension associated with progressive loss of conceptual knowledge of language.[1].
Vitamin B12 and Thiamine deficiency Thiamine deficiency may result from either chronic malnutrition or alcoholism may leads to Wernicke–Korsakoff syndrome. From them Wernicke’s encephalopathy occurs first. It has few specific features including nystagmus, ophthalmoplegia and ataxia, and an acute confusional state. If left untreated it may progress to drowsiness, coma, and even death. When wernike's encephalopathy get improve, they will develop Korsakoff amnesia.Retrograde and anterograde amnesia can be recognized. Lesions in the medial thalamus and its connections are believed to be responsible for the memory deficit. They may develop confabulation and difficulty in putting past events in the correct temporal sequence due to the involvement of the frontal fibers. Subacute combined degeneration is the commonest neurological manifestation of vitamin B 12 deficiency. It may also leads to several neuropsychiatric symptoms, but dementia due to B12 deficiency is a rare presentation.[3].
Thyroid disease Both hypothyroidism as well as hyperthyroidism have been related with reversible cognitive impairment in patients.Low thyroid hormone levels in the CNS may directly increase amyloid precursor protein expression. It may leads to A-beta production that leading to development of AD.[3].
Normal pressure hydrocephalus (NPH) It is a syndrome of gait dysfunction and enlarged cerebral ventricles in the absence of another cause.f Frontal and subcortical cognitive deficits and bladder detrusor overactivity are few other commonly manifestations of this disease. Dementia may also resulted due to NPH. The earliest features of cognitive impairment in NPH include impaired attention,visuospatial dysfunction and psychomotor slowing.[4].
References
  1. TARAWNEH R, HOLTZMAN DM. The Clinical Problem of Symptomatic Alzheimer Disease and Mild Cognitive Impairment Cold Spring Harb Perspect Med [online] 2012 May, 2(5):a006148 [viewed 12 September 2014] Available from: doi:10.1101/cshperspect.a006148
  2. RIDLEY NJ, DRAPER B, WITHALL A. Alcohol-related dementia: an update of the evidence Alzheimers Res Ther [online] , 5(1):3 [viewed 12 September 2014] Available from: doi:10.1186/alzrt157
  3. GHOSH A. Endocrine, metabolic, nutritional, and toxic disorders leading to dementia Ann Indian Acad Neurol [online] 2010 Dec, 13(Suppl2):S63-S68 [viewed 12 September 2014] Available from: doi:10.4103/0972-2327.74247
  4. SHPRECHER D, SCHWALB J, KURLAN R. Normal Pressure Hydrocephalus: Diagnosis and Treatment Curr Neurol Neurosci Rep [online] 2008 Sep, 8(5):371-376 [viewed 12 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2674287

Investigations - for Diagnosis

Fact Explanation
Plasma biomarkers Diagnosis of AD is mainly clinical, but certain other investigations are carried out to confirm the diagnosis as well as to exclude other pathologies.[1]. It is least invasive and ideal than CSF. The well studied plasma biomarker is Aβ. The major source of plasma Aβ are the peripheral tissues rather than brain. Some studies shows increased levels of Aβ1-42 or Aβ1-40 where the others found no change. And also some recent studies have shown that low plasma Aβ1-42 or Aβ1-40 levels, or Aβ1-42/Aβ1-40 ratio may be markers of future cognitive decline. Other plasma biomakers include alpha-1-antitrypsin, complement factor H, alpha-2-macroglobulin, apolipoprotein J, and apolipoprotein A–I.[2].
Cerebrospinal fluid (CSF) CSF still remains an attractive source of biomarkers for AD. There are specific and non specific cerebrospinal fluid biomarkers. The non specific once include cell counts, CSF:serum albumin ratio, and intrathecal immunoglobulin production. These are not use for diagnostic purpose but for excluding other AD mimickers. Specific biomarkers include Aβ1-42, total tau (t-tau), phosphorylated tau (p-tau),Which reflect the underlying molecular pathology of AD [2]. Disease will show decreased Aβ amyloid 42 and increased tau.[1]. Excepts those there are some novel biomakers such as Cerebrospinal fluid BACE1,Amyloid precursor protein isoforms,Biomarkers of synaptic degeneration, ect. Those are further increase the sensitivity and specificity for the early diagnosis of patients with AD.[2].
CT Neuroimaging such as CT,MRI will show gross cerebral cortical atrophy in AD.And also they are valuable for identifying some of the other causes of dementia,such as neoplasms, normal pressure hydrocephalus, and cerebral vascular disease.[1].
MRI It will also show gross cerebral cortical atrophy and valuable for identifying some of the other causes of dementia,such as neoplasms, normal pressure hydrocephalus, and cerebral vascular disease.[1]. MRI has several advantages compared with CT. They are optimal angulation of the imaging plane,excellent gray–white matter discrimination, and identification of additional vascular lesions and no bone hardening artifacts in the temporal lobe region.Automated MRI analysis can assess volumes of different brain regions including entorhinal cortex and supramarginal gyrus cortical thickness and hippocampal volumes. It is suggest that automated MRI measures can serve as noninvasive diagnostic markers for MCI and AD.[2].
Autopsy examination Neuropathologic findings on autopsy examination remain the gold standard for diagnosis of AD. Postmortem autopsy examination will show microscopic β-amyloid neuritic plaques, intraneuronal neurofibrillary tangles (containing tau protein), and amyloid angiopathy.The plaques stains positively with β amyloid antibodies and negative for prion antibodies. The numbers of plaques and tangles must exceed those found in age-matched controls without dementia.[1].
PET / Single photon emission computed tomography (SPECT) Routinely use for assessment of metabolic activity in various parts of the brain.And also useful in quantitative evaluation of physiological functions and distribution of receptors with high sensitivity.[2].
EEG EEG is used as a biomaker for the early detection and classification of dementia. Studies suggest that EEG is capable of detecting AD and VaD at early stage.And also it is useful in differentiating AD from other causes of dementia.Slowing the EEG dominant posterior rhythm frequency, increasing the diffused slow frequency, and reducing both alpha and beta activities can be seen in patients with AD.[5].
Thyroid function tests Both clinical hypothyroidism as well as hyperthyroidism is associated with reversible cognitive impairment . So that thyroid function tests are useful in assessment of patients with dementia. It has been reported that cognitive impairment is associated with both increased and decreased levels of TSH.[3].
Full blood count FBC is useful for rule out other pathologies, nutritional deficiencies lead in to anemia and infections.[3],[4].
Liver function test Carried out in dementia to exclude liver pathologies.[4].
Genetic testing However the genetics of AD are complex and not completely understood. The early-onset familial AD found to be caused by mutation in APP gene (APP). Later on presenilin 1 and 2 (PSEN1; PSEN2) were reported as novel early-onset familial AD genes on chromosomes 14 and 1. APOE gene located on chromosome 19 is another susceptible gene for late onset AD.[2].
References
  1. BIRD TD, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Alzheimer Disease Overview [online] 1993 [viewed 11 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301340
  2. MATHURANATH PS, WATTAMWAR PANDURANGR. An overview of biomarkers in Alzheimer′s disease. Ann Indian Acad Neurol [online] 2010 December [viewed 12 September 2014] Available from: doi:10.4103/0972-2327.74256
  3. GHOSH A. Endocrine, metabolic, nutritional, and toxic disorders leading to dementia Ann Indian Acad Neurol [online] 2010 Dec, 13(Suppl2):S63-S68 [viewed 12 September 2014] Available from: doi:10.4103/0972-2327.74247
  4. MACKIN P, HAMISH MCALLISTER-WILLIAMS R. Frontotemporal dementia: remembering images from the past Neuropsychiatr Dis Treat [online] 2005 Sep, 1(3):281-283 [viewed 12 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2416760
  5. AL-QAZZAZ NK, ALI SH, AHMAD SA, CHELLAPPAN K, ISLAM MS, ESCUDERO J. Role of EEG as Biomarker in the Early Detection and Classification of Dementia ScientificWorldJournal [online] 2014:906038 [viewed 13 September 2014] Available from: doi:10.1155/2014/906038

Investigations - Fitness for Management

Fact Explanation
Blood pressure Hypertension is a known risk factor for Alzheimer disease, so that Blood pressure measurement should be carried out.[1].
FBS Risk factors should be determined such as diabetes mellitus. Fasting blood sugar measurement used in that purpose.[1]
Lipid profile Lipid disorders is a causative factor for AD. Lipid profile is carried out to diagnose whether there is any associated lipid disorder.[1].
References
  1. TARAWNEH R, HOLTZMAN DM. The Clinical Problem of Symptomatic Alzheimer Disease and Mild Cognitive Impairment Cold Spring Harb Perspect Med [online] 2012 May, 2(5):a006148 [viewed 12 September 2014] Available from: doi:10.1101/cshperspect.a006148

Investigations - Followup

Fact Explanation
Mental state exam and functional and behavioral assessment Provide useful information to aid in clinical diagnosis and monitoring of disease progression in patients with dementia.Widely used screening tools in clinical practice are Mini-Mental State Exam and Clock Drawing.[1].
References
  1. TARAWNEH R, HOLTZMAN DM. The Clinical Problem of Symptomatic Alzheimer Disease and Mild Cognitive Impairment Cold Spring Harb Perspect Med [online] 2012 May, 2(5):a006148 [viewed 12 September 2014] Available from: doi:10.1101/cshperspect.a006148

Investigations - Screening/Staging

Fact Explanation
Nonspecific cerebrospinal fluid biomarkers Those include cell counts, CSF:serum albumin ratio, and intrathecal immunoglobulin production. Not specific but use for the exclusion of certain other AD mimicking conditions such as infections, inflammations, and vascular diseases. In case of vascular dementia patients usually have elevated albumin ratio, indicating impaired BBB function.[1].
Prenatal Testing Analysis of DNA extracted from fetal cells are carried out to assess whether fetus is affected or not. Amniocentesis performed at ~15-18 weeks of gestation or chorionic villus sampling performed at ~10-12 weeks’ gestation are usually carried out.[2].
Assessment of cognitive function. Useful in staging the disease. It has 3 main stages including mild,moderate and severe. Progressive decline in cognitive functions suggest severe infection.[3].
References
  1. MATHURANATH PS, WATTAMWAR PANDURANGR. An overview of biomarkers in Alzheimer′s disease. Ann Indian Acad Neurol [online] 2010 December [viewed 12 September 2014] Available from: doi:10.4103/0972-2327.74256
  2. BIRD TD, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Alzheimer Disease Overview [online] 1993 [viewed 11 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301340
  3. TARAWNEH R, HOLTZMAN DM. The Clinical Problem of Symptomatic Alzheimer Disease and Mild Cognitive Impairment Cold Spring Harb Perspect Med [online] 2012 May, 2(5):a006148 [viewed 12 September 2014] Available from: doi:10.1101/cshperspect.a006148

Management - General Measures

Fact Explanation
Supportive measures Usually the mainstay of treatment for Alzheimer disease (AD) is supportive measures.Their symptoms should be manage in an individual basis. They usually need others support and care for living or care in a nursing home. [1].
Proper diet Epidemiological studies suggest that a diet rich in fish is associated with less cognitive decline and with a decreased risk of Alzheimer's disease. Intake of fatty fish, such as tuna is found to be beneficial specially in individuals who are negative for the apolipoprotein E (ApoE) epsilon 4 allele.. Not only fish but also regular fruit and vegetable intake also reduced the risk of developing AD.[3].
Physical exercise It is beneficial in reduce the risk of dementia and AD. It is found to be improved synaptogenesis and enhanced hippocampal functioning.[3].
Genetic Counseling Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. This is carried out because AD is genetically heterogeneous, specially in the form of early-onset familial Alzheimer disease which inherited in an autosomal dominant manner. Individuals with early-onset familial Alzheimer disease have a 50% chance of transmitting the mutant allele to each child. However genetic counseling for individuals with non-familial AD and their family members is relatively non specific. They have to be informed that AD is common and the overall lifetime risk to any individual of developing dementia is approximately 10%-12%.[1].
Alzheimer's vaccine Still under development. Development of a vaccine against Alzheimer's disease have been based on two strategies. The first one is active immunotherapy using the pre-aggregated synthetic amyloid-beta42 preparation AN1792 vaccine and the other one is passive immunization using injections of already prepared polyclonal anti-beta amyloid antibodies (intravenous immunoglobulin).[3].
Proper counseling and education Educating the patient and also his or her family members about the type of disease and progression have to be carried out and have to inform the family member's that patient may need helping hand from them as well as the society.Counseling should include safety issues such as driving, financial planning, advance directives, and home arrangements.[1],[2].
References
  1. BIRD TD, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Alzheimer Disease Overview [online] 1993 [viewed 11 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301340
  2. TARAWNEH R, HOLTZMAN DM. The Clinical Problem of Symptomatic Alzheimer Disease and Mild Cognitive Impairment Cold Spring Harb Perspect Med [online] 2012 May, 2(5):a006148 [viewed 12 September 2014] Available from: doi:10.1101/cshperspect.a006148
  3. ANDRADE C, RADHAKRISHNAN R. The prevention and treatment of cognitive decline and dementia: An overview of recent research on experimental treatments Indian J Psychiatry [online] 2009, 51(1):12-25 [viewed 12 September 2014] Available from: doi:10.4103/0019-5545.44900

Management - Specific Treatments

Fact Explanation
Acetylcholinesterase inhibitors Although the exact biochemical basis of AD is not well understood, it is known that deficiencies of the brain cholinergic system and of other neurotransmitters are associated with the disease.Tacrine like drugs that increase cholinergic activity by inhibiting acetylcholinesterase produce a modest but useful behavioral or cognitive benefit in a minority of affected individuals. But it was found to be hepatotoxic. Newer such drugs such as donepezil, rivastigmine and galantamine have similar pharmocological action but not hepatotoxic.[1].
Management of sleep disturbance Pharmacological treatment is the mainstay of the short-term treatment of sleep disturbances in individuals with dementia. Variety of drugs have been used including benzodiazepines, nonbenzodiazepines,antihistamines and Antidepressants. Benzodiazepines act as decreasing sleep latency and increasing total sleep time and decreasing the amount of time spent in stage 2 sleep. But they leads to certain side effects such as increased incidence of sedation, confusion, anterograde amnesia, daytime sleepiness, and rebound insomnia. So that nonbenzodiazepines, including zolpidem, zaleplon, and eszopiclone can be use as they are having a lesser side effects and a short half life.Selective serotonin reuptake inhibitors are the most common antidepressants Prescribed and use in case of sleep disturbances secondary to depression. Exercise ,light therapy ,behavioral and multicomponent interventions are carried out as non pharmacological interventions to improve sleep.[2].
Memantine Memantine is an NMDA receptor antagonist. It has shown some effectiveness in the treatment of moderate to severe AD .[1].
Antidepressant medication They are useful in treating associated depression.[1].
Etanercept Etanercept is a TNF-alpha inhibitor, recently suggested that it may convey dramatic benefits in patients with Alzheimer's disease.[3].
Tarenflurbil It selectively targets amyloid-beta42 production. The data suggest that tarenflurbil 1600 mg/day is well tolerated and across a 2-year period. It may benefit cognition, activities of daily living, and also global functioning in patients with mild Alzheimer's disease.[3].
HMG coenzyme A reductase inhibitors and Vitamins Some reports suggest that the affected individuals taking HMG-coenzyme A reductase inhibitors for hypercholesteralemia have a reduced incidence of dementia. Vitamins and other over the counter medications also useful in treating AD.[1].
References
  1. BIRD TD, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Alzheimer Disease Overview [online] 1993 [viewed 11 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301340
  2. DESCHENES CL, MCCURRY SM. Current Treatments for Sleep Disturbances in Individuals With Dementia Curr Psychiatry Rep [online] 2009 Feb, 11(1):20-26 [viewed 12 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2649672
  3. ANDRADE C, RADHAKRISHNAN R. The prevention and treatment of cognitive decline and dementia: An overview of recent research on experimental treatments Indian J Psychiatry [online] 2009, 51(1):12-25 [viewed 12 September 2014] Available from: doi:10.4103/0019-5545.44900