Alzhemier's Disease

Tanmatra and Alzhemier’s Disease

 Ramesan Nair ,a character well depicted by Mohanlal still remains in our hearts. Yes the same Ramesan Nair from the movie " tanmatra"  through whom we came to know about the agony and hardships of the disease "Alzheimers". It is a disease which cause a gradual loss of memory with cognitive abilities. So in this blog i am going to write about the Alzheimer's disease

Alzheimer’s Disease

Alzheimer's disease is a common neurodegenerative disease responsible for 60-80% of all dementias and imposing a significant burden on developed nations. It is the result of accumulation and deposition of cerebral amyloid-β (Aβ) and is the most common Cerebral amyloid deposition disease.

Epidemiology

Alzheimer disease is the most common cause of dementia, responsible for 60-80% of all dementias .The prevalence is strongly linked to age, with >1% of 60-64-year-old patients being diagnosed with the condition, compared to 20-40% of those over 85-90 years of age .

Risk factors

Risk factors include:-

· Advanced age

· Female gender

· Current smoking

· Family history of dementia

· Mutations of amyloid precursor protein

· Down syndrome

· Chronic inflammation

In addition to the genetic and environmental factors above, the age of presentation is also influenced by socioeconomic factors

· Formal education

· Income

· Occupational status

· Social network and family support

Individuals with premorbid higher function/supports are able to compensate for early disease changes to a greater degree and thus present later. Consequently, when well-supported patients eventually present, they tend to have more marked morphological changes on imaging

Clinical presentation

Traditionally, Alzheimer disease has been clinically characterized predominantly by memory deficits, at least in initial stages. It has become increasingly evident that in addition to the typical presentation, a number of atypical clinical patterns exist, which are nonetheless pathologically Alzheimer disease.

Classical/typical Alzheimer disease

The typical patient with Alzheimer disease will present initially with antegrade episodic memory deficits . Over time (often years), the disease progresses, with eventual involvement of attentional and executive processes, semantic memory, praxis, and visuoperceptual abilities. Neuropsychiatric symptoms are also common and eventually affect almost all patients. These include apathy, depression, anxiety, aggression/agitation, and  psychosis(delusions and hallucinations) 

Atypical/variant Alzheimer disease

These entities, often recognized clinically well before they were identified to be pathologically identical to Alzheimer disease, are characterized by slowly progressive focal cortical atrophy, with symptoms and signs matched to the affected area. Examples include

·       Posterior cortical atrophy

·       Frontal variant of Alzheimer disease

·       Minority of cases with predominant semantic dementia

Stages of Alzheimer's disease

 

1.Effect of aging on memory  but not AD

·  Forgetting things occasionally

· Misplacing items sometimes 

· Minor short term memory loss

· Not remembering exact details

 

2.Early stage Alzheimer's

·       Not remembering episodes of forgetfulness

·       Forgets names of family or friends

·       Changes may only be noticed by close friends or relatives

·       Some confusion in situations outside the familiar

 

3.Middle stage Alzheimer's

· Greater difficulty remembering recently learned information

· Deepening confusion in many circumstances

· Problems with sleep

·Trouble determining their location

 

4.Late stage Alzheimer's

·       Poor ability to think

·       Problems speaking

·       Repeats same conversations

·       More abusive, anxious, or paranoid

 

Diagnosis

Clinical diagnosis is made by identifying a progressive decline in memory both with clinical examinations and neuropsychologic tests and has been historically based on the NINCDS-ADRA criteria, which divides patients according to the certainty of the diagnosis into:

1. Definite: clinical diagnosis and histologic confirmation

2. Probable: typical clinical syndrome without histologic confirmation 81% sensitive, 73% specific 

3. Possible: atypical clinical features without histologic confirmation but no alternative diagnosis 

Although using longitudinal clinical criteria is highly sensitive in diagnosing a dementia of any type (>90%), they are relatively inaccurate (<70%) in diagnosing Alzheimer disease specifically.

Importantly, NINCDS-ADRA criteria the  only include imaging and laboratory examination or blood and CSF in excluding other causes.

The only definitive diagnostic test is brain biopsy which in practice is rarely obtained. As such, the combination of clinical features and neuroimaging are usually considered sufficient, although, especially with the recognition of variants, this approach undoubtedly misdiagnoses a significant number of cases.

Pathology

Alzheimer disease is characterized by the accumulation within the brain of cerebral amyloid-β forming neuritic plaques,neurofibrillary tangles and eventually progressive loss of neurons.

Cerebral amyloid-β particularly deposits in association areas of the neocortex, the posterior cingulate and precuneus, as well as the limbic cortex, although the reason for this distribution has not been elucidated.

The underlying reason for the accumulation of senile (neuritic) plaques and neurofibrillary tangles remains poorly understood, as does the reason for non-uniform distribution in the cortex.

There is, however, increasing evidence to suggest that chronic inflammation is at least partially responsible. Such inflammation can lead to prolonged parenchymal activation of microglial cells which in turn results in the release of inflammatory mediators with subsequent neuronal damage and amyloid-induced neurodegeneration. 

Treatment and prognosis

·       There is no cure for this disease; some drugs have been developed trying to improve symptoms or, at least, temporarily slow down their progression.

·       Cholinesterase inhibitors e.g. donepezil

·       Partial NMDA receptor antagonists

·       Medications for behavioral symptoms

1.    Antidepressants

2.    Anxiolytics

3.    Antiparkinsonian (movement symptoms)

4.    Anticonvulsants/sedatives (behavioral)

  Conclusion

Alzheimer’s is a family disease…it requires countless hours of care, which are typically provided by family caregivers…without professional help,it can be impossible to juggle providing that care with jobs,raising kids or just time for yourself