Alzheimer disease is Senile Dementia of the Alzheimer Type (SDAT) or simply Alzheimer's is the most characteristic form of dementia. This is irremediable, degenerative, and terminal disease was first explicate by German psychiatrist and neuropathologist Alois Alzheimer in 1906 and named after him. Primarily, it is identified in people over 65 years of age, although the less-prevalent early-onset Alzheimer's can occur much earlier.
The cause of seldom form of the disease is not known; mostly this is due to heterogeneous caused by ageing unanimity with complex interaction of genetic and environmental factors. It is characterized as a slow progressive diminish in cognitive and psych behavior .Alzheimer's disease is most expensive in relation with the diagnosing and treatment as it involves caregivers, nursing home treatment reviewing the treatment as this is an degenerative so supervision of the patient should be considered .
Symptoms of Alzheimer's disease :-
Although the sequence of Alzheimer's disease is unprecedented for individual to individual, there are many common symptoms. The initial characterized symptoms are often mistakenly thought to be 'age-related', or due to instance of stress. In the early stages, the most commonly admit symptom is inability to gain new memories, such as difficulty in retain recently observed facts. When AD is suspected, the diagnosis is usually done with behavioral assessments and cognitive tests. As the disease progress , symptoms include confusion, irritability and aggression, mood swings, language breakdown, long-term memory loss, and the general withdrawal of the sufferer as their senses decline. Constantly , bodily functions are lost, ultimately causing to death. Individual prognosis is tough to assess, as the duration of the disease varies. AD develops for an undefined period of time before becoming fully apparent, and it can progress undetectable for years.
The disease progression is organized in to seven different stages :-
Stage 1: No cognitive impairment
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Healthy individuals experience no memory problems and none are distant to a health care professional during a medical consultation.
Stage 2: Very mild decline
Individuals at this point feel as if they have memory loss, forgetting known words or names or the location of keys, eyeglasses or other everyday objects. But these problems are not clear during a medical examination or observable to friends, family or co-workers.
Stage 3: Mild cognitive decline
Early-stage Alzheimer's can be detected in some, but not all, individuals with these signs
Friends, family or co-workers begin to advice deficiencies. Problems with memory or concentration may be perceptible in clinical testing or visible during a detailed medical interview. Common difficulties insert:
• Word- or name-finding complication noticeable to family or close associates
• Declined ability to memorize names when introduced to new people
Efficacy issues in social and work settings prominent to others
• Reading a passage and remembering little material
• displace or loosing a valuable object
• Decrease in ability to organize
Stage 4: Moderate cognitive decline
(Mild or early-stage Alzheimer's disease)
At this stage, a careful medical interview identifies evident deficiencies in the following areas:
• Decreased acquaintance of recent happenings
• broken ability to fulfill challenging mental arithmetic
•impaired capacity to perform complex works, such as marketing, planning dinner for guests, or paying bills and handling finances
• Reduced cognizance of personal history
• The overwhelmed individual may seem repentant and uncommunicative especially in socially or mentally challenging position.
Stage 5: Moderately severe cognitive decline
(Moderate or mid-stage Alzheimer's disease)
Major interval in memory and lack in cognitive function proceed. Some cooperation with day-to-day activities becomes essential. At this stage, individuals may:
• Be inefficient during a medical interview to extract s important details as their current address, their telephone number, or the name of the college or high school they graduated
• Become bewildered about where they are or about the date, day of the week or season
• Have stress with less challenging mental arithmetic; for example, counting backward from 40 by 4s or from 20 by 2s
• Usually keeps substantial knowledge about themselves and know their own name and the names of their spouse or children
Always on Time
Marked to Standard
• Usually require no help with eating or using the toilet
Stage 6: Severe cognitive decline
(Moderately severe or mid-stage Alzheimer's disease)
Memory discordance continue to descend, significant personality changes may raise, and affected individuals need extended help with daily activities. At this stage, individuals may:
• Lose most information of recent experiences and events as well as of their surroundings
• Recollect their personal history inadequately, although they generally recall their own name
• Occasionally ignore the name of their spouse or primary caregiver but generally can differ familiar from unfamiliar faces
• Need assistance to get dressed properly; without supervision, may make such misconception as putting pajamas over daytime clothes or shoes on wrong feet
• Need help with dealing details of toileting (flushing toilet, wiping and disposing of tissue properly)
• Have increasing occurrence of urinary or fecal unrestraint
• Experience serious personality changes and behavioral symptoms, including dubious and delusions (for example, believing that their caregiver is an hypocrite); hallucination; or compulsive, repetitive behaviors such as hand-wringing or tissue shredding
• Tend to peregrinate and become lost
Stage 7: Very severe cognitive decline
(Severe or late-stage Alzheimer's disease)
This is the last stage of the disease when individuals lose the capability to answer to their environment, the ability to speak, and, sooner or later, the ability to control movement.
• Naturally individuals lose their capacity for recognizable speech, although words or phrases may be pronounced
• Individuals need guidance with eating and toileting and there is general actions.
• Individuals lose the capacity to walk without assistance, then the ability to sit without support, the ability to laugh, and the ability to hold their head up. Reflexes become atypical and muscles grow stiff. Swallowing is weakened
The pathophysiologic aspects of Alzheimer disease include neruropathologic and neurotransmitter changes .Alzheimer disease is characterized by cortical atrophy and loss of neurons,particularly in parietal and temporal lobes .with significant atrophy there is ventricular enlargement from the loss of brain tissue. The exact cause of the disease is still yet to confirm .it is likely that Alzheimer disease is caused by several factors that interact differently in different persons.
Alzheimer disease is essentially a diagnosis of exclusion .there is no peripheral biochemical markers or tests for the disease .the diagnosis can be confirmed only by microscopic examination of the brain tissue obtained from a cerebral biopsy or at autopsy. The diagnosis is based on clinical findings,diagnosis of Alzheimer disease requires the presence of dementia established by clinical examination and documented by results of
.MMSE -Mean mental state examination
.ADAS -cog--- Alzheimer's disease assessment scale cognitive scale
. CDR---clinical Dementia rating scale
.DAD-Disability assessment for dementia
.MDS-ADL---Minimum data set-activities of daily living activities
Drugs and treatment for Alzheimer's disease:-
There is no curative treatment for deminentia .Drugs are used primarily to slow the progression and to control depression, agitation, or sleep disorder .The main two class of drugs cholinesterase inhibitors and N-methyl-D-aspartate show promising in terms of slowing the progression of the disease .
Other treatments for Alzheimer's disease include agents that are thought to have neuro-protective effects, psychotropic medication such as antipsychotics and mood stabilizers which help in behavioral management of the disease.
Drugs used for the treatment of disease
Classification of Alzheimer's disease
Used in stages
Acetyl cholinesterase inhibitors
Mild to moderate
Mild to moderate
Mild to moderate
Mild to moderate
Moderate to mild
The term clinical trial involves a number of detail issues of safety and efficacy data to be collected for health interventions (e.g., drugs, diagnostics, devices, therapy protocols). These trials can be done only after adequate data has been gathered on the quality of the non-clinical safety and approved by the authorized and governing body of the health system.
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Depending on the type of drug or therapy protocol and the stage of its development, investigators screens healthy volunteers and/or patients into small groups initially, followed by larger scale studies in patients that often compare the new product with the currently prescribed treatment for several months to years. As positive safety and efficacy data are gathered, and data is reviewed for results on the existing data.
Based on the number of patients and the testing pattern the clinical trials are further classified in to four phases
Phase 1 clinical trials:-
Clinical trials done for the new drug on small group people around 20-80 to evaluate the safety and to identify the drug caused side effects
Phase 2 clinical trails:-
Clinical trials in this phase conducted to evaluate further safety issues on group of people 100-300.
Phase 3 clinical trials:-
A large pool of people of 1000-3000 are audited for effectiveness and observe adverse effects and the data or the report is summarized which allows to deal with safety issues
Phase 4 clinical trials:-
These studies done after the drug reached in to the market to evaluate the treatment effects on various populations and to access the side effects associated with long-term use
Clinical trials Meta-Analysis:-
A number of clinical trials have been conducted on an approved drug around the globe .To check the safety and efficacy and to check the genetical factor which varies a continent to continent ,which leads to the generation of multifold data which gives facts of the trials conducted ,but this data varies from one method to the other leads to confusion with the results.
On detail verification and analyzing clinical trial data details from the published data or unpublished data available on electronic databases (for example, MEDLINE, EMBASE,Cochrane Central Register of Controlled Trials) and journals search. Investigating the findings of these data helps in the improvement of the trials pattern and through knowledge of efficacy and adverse effects.
Meta-analysis defined by Huque: ''A statistical analysis that combines or integrates the results of several independent clinical trials considered by the analyst to be combinable.''
Meta-analysis term denotes for illuminate a possible ingredient of systematic reviews, and distinguishing between the two terms contributes to methodological clarity.
Benefits of Meta-Analysis in clinical trial:-
Helps in finding clinical effectiveness of healthcare interventions by analyzing two or more randomized trails.
Precise estimation of treatment effect can be analyzed under different protocols.
Complete coverage of all issues in different study investigates the presence of heterogeneity and scrutinize powerful findings of different trials.
It offers a impartial and helpful way of dealing with number of practical tribulation that beset anyone trying to make sense of effectiveness research.
Meta-analysis offers an complete study of the clinical research without involving in clinical trial procedures.
Meta-analysis evidently has dominance over conventional narrative reviews and carries significant promise as a tool in clinical research and health technology evaluation.
META-ANALYSIA OF ALZHEIMER'S DISEASE drugs :-
the class of drugs used for the treatment of alzheimer's disease are
Acetyl cholinesterase inhibitors(AChEI)
Acetyl cholinesterase inhibitors(AChEI):-
It is hypothesized that suppression of acetyl cholinesterase (AChE) within the CNS will boost cholinergic transmission, at least at those neurons that are still functioning. Reversible AChE inhibitors available for the treatment of mild to moderate Alzheimer's disease, they are donepezil, galantamine, rivastigmine, and tacrine. Donepizil, Rivastigmine are uncompetitive inhibitors where as galantamine is competitive inhibitor of AChE and appear to have some selectivity for AChE in the CNS as compared to the periphery. Galantamine may also be acting as an allosteric modulator of the nicotinic receptor in the CNS and, therefore, secondarily increase cholinergic neurotransmission through a separate mechanism. These compounds help to improve the cognitive functioning in Alzheimer's patient's .Due to adverse effects displayed by the tacrine, currently it is not prescribed.
Cholinesterase inhibitors reduces the formation or neurotoxicity of Aβ which setbacks the progression of AD as well as producing symptomatic effect.
Type of inhibition
Duration of action
Main side effects
Short acting,revesible affects both AChE and BuChe
Cholinergic side effects ,hepatotoxicicity
Not prescribed now due to toxicity
Short acting ,reversible AChE -selective
agitation and aggression reported on use
60-90 pounds for 28 tablets
Slowly reversible affects both AChE and BuChE
Cholinergic effects on prolong use
Dose escalation is needed to inhibit adverse effects
70-85 pounds for 28 tablets depending on the mode of release
Reversible ,non-selective, also enhances nictonic acetylcholine receptor activation by allosteric mechanism
Few side effects
68.04 pounds for 56 tablets