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150]

Review Article

Memory Impairment With Reference to Alzheimer’s Disease:

An Update
Jyoti Gupta, Mayank Kulshreshtha
Department of Pharmacology, School of Pharmacy, Babu Banarasi Das University, Lucknow, Uttar Pradesh, India

Abstract
Dementia or memory loss is the hallmark symptom of Alzheimer’s disease (AD). The exploration of AD helps to identify the problems
involved in neural structures such as the default network and role of genetic factors. Episodic memory (EM) directly deals with the memory
system that allows an individual to consciously retrieve an old experience or an episode of life. EM plays an important role in AD. The World
Health Organization predicts that, by 2025, about 75% of the estimated 1.2 billion people aged 60 years and older will reside in developing
countries. It is estimated that the number of people living with dementia will almost double every 20 years to 42.3 million in 2020 and 81.1
million in 2040. In India, there are lesser number of good quality scientific studies/researches that deal with the real trend of the disease and
determine the mechanism involved, risk factors, investigations on dementia, decline in awareness, and inadequate availability of social
benefit. India is a country with varied cultures, and, therefore, conducting a genetic epidemiological study here has greater advantage. The goal
of this review is to provide knowledge and increase the awareness of dementia associated with AD, as well as to understand the mechanism
involved and its treatment, which can be useful for researchers or scientists in the near future.

Keywords: Alzheimer’s disease, dementia, episodic memory, World Health Organization

INTRODUCTION consist of a cell body, axons, and dendrites and play a

Nervous system and brain
Nervous system is divided into two parts, that is, the
central nervous system (CNS) and peripheral nervous
system (PNS). The CNS is composed of the brain and
spinal cord, whereas the PNS is composed of the spinal
nerves that branch from the brain.[1] The cerebrum is the
largest part of the brain, and it is made up of the right
hemisphere and left hemisphere. It has many functions
such as vision, hearing, learning, emotions, and fine
control movement.[2] The brainstem includes the
midbrain (mesencephalon), which is a relatively narrow
band of the brainstem surrounding the cerebral aqueduct.
Pons (metencephalon) is located below the cerebellum, its
ventral bulge it means pons is clearly visible, and the
medulla oblongata (myelencephalon) extends from the
inferior pontine sulcus to the spinal cord. It mostly
performs automatic functions such as breathing, heart
rate control, body temperature regulation, sneezing, and
coughing.[3] The brain is made up of two types of cells,
that is, the nerve cells and glial cells. The nerve cells
specific role when conveying message or information
through chemical and electrical signals. Glial (Greek
word meaning glue) cells are the cells of the brain that
provide the neurons with nourishment, protection, and
structural support.[1]
MEMORY
Memory is an important function of the brain and is the
ability of an individual to record information, retain and
recall them whenever needed, and, moreover, the use this
information to adapt one’s responses to the environment;
hence, it is vital for survival.[4] It is also defined as the
special facility of the brain that retains the events
developed during the process of learning and mediated
Address for correspondence: Assistant Professor, Mayank Kulshreshtha,
Department of Pharmacology, School of Pharmacy, Babu Banarasi Das
University, Lucknow, Uttar Pradesh, India.
E-mail: professormayank@gmail.com

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DOI: How to cite this article: Gupta J, Kulshreshtha M. Memory Impairment

10.4103/ijnpnd.ijnpnd_7_17 With Reference to Alzheimer’s Disease: An Update. Int J Nutr Pharmacol
Neurol Dis 2017;7:45-53.

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Gupta and Kulshreshtha: Memory impairment with reference to Alzheimer’s disease

by the nervous system. Learning is defined as the ability to AMNESIA

alter behavior on the basis of experience.[5]
Memory is the ability of an individual to record sensory
stimuli, events, information, etc. Learning is the process of
acquiring knowledge about the world, whereas memory could
be considered as the retention of the acquired knowledge.[6]
Memory refers to the persistence of learning that can be
revealed at a later time, whereas learning is defined as the
process of acquiring new information or skills. Memory is the
usual consequence of learning and reflects the enduring
changes in the nervous system that result from transient
experiences.[7] Memory loss, also called amnesia, happens
when a person loses the ability to remember information and
events they would normally be able to recall. Memory loss
due to the dysfunction of the episodic memory (EM) system
generally follows a pattern known as Ribot’s law, which
states that events just prior to an ictus are most vulnerable to
decay, whereas remote memories are more resistant.[8] The
memory system and its anatomical structures are given in
Table 1.
DEMENTIA
Dementia is defined as an acquired deterioration in
cognitive abilities that impair the successful performance
of activities of daily living. Neuropsychiatric and
social deficits also develop in many dementia syndromes
resulting in depression, withdrawal, hallucinations,
delusions, agitation, insomnia, and disinhibition.[9]
Dementia is a mental disorder characterized by the loss
of intellectual ability, which is sufficiently severe to
interfere with one’s social and occupational activity.[10]
Dementia is characterized by the presence of
memory impairment in the presence of other cognitive
defects. The different types of dementia are listed in
Table 2.[11-14]
Amnesia also known as amnesic syndrome is a deficit in
memory caused by brain damage, disease, or psychological
trauma. Essentially, amnesia is loss in memory. The memory
can be either wholly or partially lost due to the extent of
damage that was caused, and that damage is associated with
damage to the medial temporal lobe.[15] There are two
main types of amnesia: retrograde amnesia and
anterograde amnesia.
Retrograde amnesia
Retrograde amnesia is the inability to retrieve information
that was acquired before a particular date, usually the date of
an accident or operation. Retrograde memory loss almost
always occurs in association with anterograde amnesia, which
is characterized by an inability to learn new information.[16]
Anterograde amnesia
Anterograde amnesia is the inability to transfer new
information from the short-term store to the long-term
store.[17]
APHASIA
The neural substrate of language is composed of a
distributed network centered in the perisylvian region of
the left hemisphere. The posterior pole of this network is
located at the temporoparietal junction and includes a region
known as Wernicke’s area. An essential function of
Wernicke’s area is to transform sensory inputs into their
lexical representations so that these can establish the
distributed associations that give the word its meaning.
The anterior pole of the language network is located in
the inferior frontal gyrus and includes the region called as
Broca’s area. Wernicke’s and Broca’s areas are

Table 1: The memory system and its anatomy

Memory system Examples Awareness Length of storage Major anatomical
structures
Episodic memory Deals with short stories Explicit declarative Some minutes to many Medial temporal lobe,
such as what you had years anterior thalamic nucleus,
worn last night mammillary body, fornix, and
prefrontal cortex
Semantic memory Deals with information Explicit declarative Some minutes to many Inferior lateral temporal lobes
such as how a fork and years
comb are different
Autonomic simple Pavlov’s dog; a fear Implicit nondeclarative Minutes to years Amygdala and basolateral
classical condition response limbic system
Motoric simple Eye-blink conditioning Implicit nondeclarative Minutes to months Cerebellum
classical condition
Procedural memory Driving a standard Implicit nondeclarative Minutes to years Basal ganglia, cerebellum,
Transmission car and supplementary motor area
Conceptual memory Word-stem completion Implicit nondeclarative Minutes to days Inferior prefrontal cortex
Phonological: prefrontal
cortex, Broca’s area

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Gupta and Kulshreshtha: Memory impairment with reference to Alzheimer’s disease

interconnected with each other and with additional
perisylvian, temporal, prefrontal, and posterior
parietal regions making up a neural network subserving
the various aspects of language function. Damage
to any one of these components, because their
interconnections can give rise to language disturbances, is
called as aphasia.[18] Different types of aphasia are
Wernicke’s aphasia, Broca’s aphasia, global aphasia,
conduction aphasia, isolation aphasia, and anomic
aphasia, as listed in Table 3.[19-21]
APHEMIA
There is an acute or severely impaired fluency, which cannot
be accounted for by corticobulbar, cerebellar, or
extrapyramidal dysfunction. Writing, reading, and compre-
hensions are intact; therefore, this is not a true aphasic
syndrome.[22]
Signs and symptoms
Memory impairment is the hallmark symptom of Alzheimer’s
disease (AD) and usually involves behaviors such as
forgotten appointments, straying away from home,
misplaced items, and repetitive questions. Along with
memory problems, AD can be recognized by insomnia,
anxiety, depression, disruptive behavior, and
hallucinations. Several studies have found evidence that
AD is a disease that is caused by or is a result of
decreased metabolic activity in the brain.[23] Figure 1
shows the difference between the brain from a healthy
patient and the brain from a patient with AD. The
deposition of protein amyloid (brain) is noticed in different
forms of AD. It is composed of a secreted peptide (A) that can
be either 40 or 42 amino acids long (A 1–40 or A 1–42). A
1–42 forms insoluble amyloid fibrils and is deposited early
and selectively in the senile plaques that are a pathological
hallmark of AD.[24]

Table 2: Different types of dementia

Type of dementia Description
Vascular dementia In this condition, thinking power is declined due to decreased blood supply to the brain, which kills the cells
present anywhere in the body
Frontotemporal dementia (FTD) FTD deals with a group of disorders caused by the loss of nerve cells in the brain area (frontal lobe and
temporal lobe). This leads to a loss of function in this area such as deterioration in behavior, personality,
language disturbances, and alterations in the muscle or motor functions
Dementia with Lewy bodies DLB is a type of progressive dementia that leads to a decline in thinking, reasoning, and independent function
(DLBs) because of abnormal microscopic deposits that damage the brain cells over time
Cognitive impairment with no Characterized by lower cognitive performance than would be expected given the age and educational attainment
dementia (CIND) of the person
AD It is a neurodegenerative disorder and the most common form of dementia that leads to memory impairment. It
is named after the German physician Aloes Alzheimer
Chronic traumatic encephalopathy CTE is a brain condition associated with repeated blows to the head. Potential signs of the disease are problems
(CTE) with thinking and memory, personality changes, and behavioral changes including aggression and depression
Creutzfeldt–Jakob disease (CJD) CJD is the most common human form of a group of rare, fatal brain disorders known as prion diseases which is
found throughout the body but whose normal function is not yet known. The prions begin folding into an
abnormal three-dimensional shape
Huntington’s disease It is a progressive brain disorder caused by a single defective gene on chromosome 4
Wernicke–Korsakoff syndrome It is a chronic memory disorder caused by severe deficiency of thiamine. The most common cause is alcohol
misuse
Mixed dementia Abnormalities are linked to more than one cause of dementia and occur simultaneously in the brain
PD It often results in a progressive dementia similar to DLBs or Alzheimer’s

Table 3: Different types of aphasia

Type of Description
aphasia
Wernicke’s This aphasia has expressive as well as receptive components. Repetition, naming, reading, and writing are also impaired
aphasia
Broca’s aphasia The last two features indicate that Broca’s aphasia is not just an “expressive” or “motor” disorder, but that it may also involve a
comprehension deficit for function words and syntax
Global aphasia This syndrome represents the combined dysfunction of Broca’s and Wernicke’s areas and usually results from strokes that involve
the entire middle cerebral artery distribution in the left hemisphere
Conduction The paraphasic output in conduction aphasia interferes with the ability to express meaning, but this deficit is not nearly as severe
aphasia as the one displayed by patients with Wernicke’s aphasia
Alzheimer’s It is a neurodegenerative disorder and the most common form of dementia that leads to memory impairment. It is named after the
disease German physician Aloes Alzheimer

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Gupta and Kulshreshtha: Memory impairment with reference to Alzheimer’s disease

Figure 1: The difference between the brain of a healthy patient and the brain of a patient with Alzheimer’s brain

Memory impairment has been classified into three stages and (1) Brain tumor.
each stage has its specific symptoms. (2) Cancer treatment such as brain radiation, bone marrow
(1) Stage one usually lasts for 2–4 years. It involves transplant, or chemotherapy.
confusion, forgetfulness, disorientation, recent (3) Migraine headache.
memory loss, and mood changes. (4) Not enough oxygen getting to the brain when your heart
(2) Stage two often lasts for 2–10 years. It is typically or breathing is stopped for too long.
characterized by decreased memory, reduced attention (5) Severe brain infection or infection around the brain.
span, hallucinations, restlessness, muscle spasms, (6) Major surgery or severe illness including brain surgery.
reduced ability to perform logical activities, (7) Transient global amnesia (sudden, temporary loss of
increased irritability, and increased inability to memory) of unclear cause.
organize thoughts. (8) Transient ischemic attack or stroke.
(3) Stage three generally lasts for 1–3 years with risk factors
that include age, head injury, and most often also Sometimes, memory loss occurs with mental health
involving incontinence, swallowing difficulty, the problems, such as the following:
development of skin infections, and seizures.[25] (1) After a major, traumatic or stressful event.
(2) Bipolar disorder.
Causes (3) Depression or other mental health disorders such as
schizophrenia.
Normal aging can cause some forgetfulness. It is normal to
have some trouble learning new material or needing more
time to remember it. However, normal aging does not lead to Memory loss may be a sign of dementia. Dementia also
dramatic memory loss. Such memory loss is due to other affects thinking, language, judgment, and behavior. Other
diseases.[26] Many areas of the brain help create and retrieve causes of memory loss include the following:[26-29]
memories. A problem in any of these areas can lead to (1) Alcohol or use of illegal drugs.
memory loss. Memory loss may result from a new injury (2) Brain infections such as Lyme disease, syphilis, or human
to the brain, which is caused by or is present after the immunodeficiency virus (HIV)/acquired immune
following: deficiency syndrome (AIDS).

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Gupta and Kulshreshtha: Memory impairment with reference to Alzheimer’s disease
(3) Overuse of medicines such as barbiturates or
antidepressant drug.
(4) Electroconvulsive therapy (most often short-term
memory loss).
(5) Epilepsy that is not well controlled. Illness that results in
the loss of or damage to brain tissue or nerve cells such
as Parkinson’s disease (PD), Huntington’s disease
(HD), or multiple sclerosis.
(6) Low levels of important nutrients or vitamins such as
low Vitamin B12.
EPIDEMIOLOGY
Worldwide, an estimated 35.6 million people were
living with dementia in 2010. This number is estimated
to nearly double every 20 years, to 65.7 million in 2030
and 115.4 million in 2050.[30] Census reports indicate that
the Indian population has approximately tripled during the
last 50 years, but the number of elderly Indians has
increased more than fourfold. When considering
the continuation of the trend, the United Nation predicts
that the Indian population will again grow by 50%
in the next 50 years.[31] Epidemiological studies found a
significant correlation between the dietary intake of
vegetables and improvement in cognitive function
in the elderly. For instance, aging women consuming
cruciferous vegetables (e.g., broccoli and cauliflower)
showed less cognitive decline than those not consuming
them.[32] Several meta-analyses have resulted in
roughly similar estimates of dementia prevalence across
regions. The estimated global dementia prevalence in
people aged over 60 is approximately 3.9%, with the
regional prevalence being 1.6% in Africa, 3.9% in
Eastern Europe, 4.0% in China, 4.6% in Latin
America, 5.4% in Western Europe, and 6.4% in North
America.[33] The global annual incidence of dementia is
estimated to be around 7.5 per 1000 population.[34] The
United Nations estimated that the number of people
suffering from age-related neurodegeneration,
particularly from AD, will exponentially increase from
25.5 million in 2000 to an estimated 114
million in 2050.[35] Several meta-analyses have resulted
in roughly similar estimates of dementia prevalence
across regions. The estimated global dementia
prevalence in people aged over 60 is approximately
3.9%, with the regional prevalence being
1.6% in Africa, 3.9% in Eastern Europe, 4.0% in China,
4.6% in Latin America, and 5.4% in Western. The
incidence rate of dementia increases exponentially with
age, and incidence rates across regions of dementia are
quite similar.[33]
Hence, the global trend in the phenomenon of
population aging has dramatic consequences for
public health, healthcare financing, and delivery
systems in the world and, especially, in developing
countries.[36]
International Journal of Nutrition, Pharmacology, Neurological Diseases ¦ Volume 7 ¦ Issue 3 ¦ July-September 2017
EVALUATION OF MEMORY IMPAIRMENT
Physical and neurological examination
A thorough general and neurological examination is essential
to document the presence of dementia, look for other signs of
nervous system involvement, and search for clues suggesting
a systematic disease that might be responsible for cognitive
disorders. The examination considers the following aspects:
(1) AD does not affect the motor system until later in the
course; in contrast, patients with frontotemporal dementia
(FTD) often develop axial rigidity, supranuclear gaze
palsy, or features of amyotrophic lateral sclerosis.
(2) Dementia with Lewy bodies (DLBs) may have initial
symptoms such as the new onset of a Parkinsonism
syndrome (resting, tremor, bradykinesia, and festinating
gait) with dementia.
(3) Corticobasal degeneration (CBD) is associated with
dystonia, alien hand, and asymmetric extrapyramidal,
pyramidal, or sensory deficits or myoclonus.
(4) Progressive supranuclear palsy (PSP) is associated with
unexplained falls, axial rigidity, dysphagia, and vertical
gaze deficits.
(5) Creutzfeldt–Jakob disease (CJD) is suggested by the
presence of diffuse rigidity, a kinetic state, and
myoclonus.[9]
Several neurological features which affect the dementia,
cognition and AD, i.e., extrapyramidal, bradykinesia,
rigidity, tremor, chorea and these are associated with the
PD, CBD, PSP, FTP, DLBs, VD, HD.[37]
Cognitive and neuropsychiatric examination
(1) Brief screening tools such as the mini-mental state
examination (MMSE) help to confirm the presence of
cognitive impairment and to follow the progression of
dementia.
(2) The MMSE, an easily administered 30-point test of
cognitive function, contains a test of orientation,
working memory, language comprehension, naming,
and copying.
(3) In FTD, the earliest deficit often involves frontal
executive or language function.
(4) Patients with DLB have more severe deficits in
visuospatial function but perform better on EM tasks
than patients with AD.
(5) In delirium, deficits tend to fall in the area of attention,
working memory, and frontal function.[38]
Clinical manifestation
(1) The cognitive changes with AD tend to follow a
characteristic pattern, beginning with memory
impairment and spreading to language and
visuospatial deficits.
(2) However, 20% of patients with AD present with
nonmemory complaints such as word finding,
organizational, and navigational difficulties.
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Gupta and Kulshreshtha: Memory impairment with reference to Alzheimer’s disease
(3) Delusions are common and usually simple in quality
such as delusions of theft, infidelity, or
misidentification.[39]
Pathophysiological Discussion of Synapses Where
Memory is Stored
Synaptic plasticity refers to the changes in the strength of
synaptic function, and this process is currently a major focus
of research on the neurobiology of learning and memory.[39]
Synaptic plasticity includes both short-term changes in the
strength or efficacy of neurotransmission as well as longer-
term changes in the structure and number of synapses.[40]
The experimental models of changes in synaptic strength or
effectiveness in response to repeated electrical stimulation are
thought to mimic physiologic plasticity. These changes are
referred to as long-term potentiation (LTP) when synaptic
strength increases or long-term depression (LTD) when it
decreases. These modifications in synaptic strength, both
positive and negative, distributed across thousands to
millions of connections among neurons, are believed to
form the physical and biochemical substrate for memory
and learning.[41] Short-term memory, generally, does not
require protein synthesis but results from changes in
synaptic strength within synapses, whereas in the case of
long-term memory, storage, generally, requires the
transcription and translation of a new protein that enhances
the strength or number of active synapses.[42]
SIGNALING PATHWAY OF LEARNING AND MEMORY
SYSTEM
Multiple synaptic signal transduction pathways contribute to
the reinforcement of a memory by multiple sensory stimuli,
for example, sound, sight, and taste. The following three types
of neurotransmitter receptors are shown: inotropic receptors
that open ion channels (e.g., the N-methyl-d-aspartate
receptor (NMDA) and -amino-3-hydroxy-5-methyl-4-
ioxazolepropionic acid (AMPA)-type glutamate receptors
shown at top left), metabotropic receptors (e.g., for
glutamate, acetylcholine, and serotonin at upper right)
linked to synthesis of inositol phosphates and stimulation
of protein kinase C (PKC), and transmembrane receptors
linked to the generation of cyclic adenosine monophosphate
(cAMP), shown at upper far right. Most long-term memories
require gene transcription and translation of new protein,
whereas short-term memories can result from local synaptic
changes, for example, phosphorylation and/or addition of
AMPA-type glutamate receptors shown at the upper left.
Cross-talk among the pathways contributes to synergism
among stimuli and also provides redundancy if one
pathway is affected by genetic or acquired disorders.[43]
Memory loss is associated with brain shrinkage and
localized loss of neurons, mainly in the hippocampus and
basal forebrain. The loss of cholinergic neurons in the
hippocampus and frontal cortex is a feature of the disease
and is thought to underlie the cognitive deficit and loss of
50 International Journal of Nutrition, Pharmacology, Neurological Diseases ¦ Volume 7 ¦ Issue 3 ¦ July-September 2017
short-term memory that occur in AD. The main pathological
features of memory loss and AD comprise amyloid plaques
(APs), neurofibrillary tangles, and a loss of neurons
(particularly the cholinergic neurons of the basal
forebrain). The AD neuropathologic change is now ranked
on three parameters (Amyloid, Braak, CERAD) to obtain an
“ABC” score: histopathologic assessments of beta-amyloid
(A)-containing amyloid plaques (A), Braak staging of
neurofibrillary tangles (B), and scoring of neuritic amyloid
plaques (C). AP consists of aggregates of the A fragment of
amyloid precursor protein, a normal neuronal membrane
protein, produced by the action of the alpha and beta
secretease. AD-associated excessive A formation results in
neurotoxicity.[44]
MEMORY CELLS, NEUROTRANSMITTERS, AND GROWTH
FACTORS INVOLVED IN MEMORY IMPAIRMENT
Acetylcholine is the most important neurotransmitter
involved in the regulation of neurotransmission of
cognitive impairment or its functions. Cholinergic
transmission is terminated by acetylcholine hydrolysis
through the enzyme acetylcholinesterase (AChE), which
is responsible for the degradation of acetylcholine to
acetate and choiline in the synaptic cleft. According to
the cholinergic hypothesis, memory impairment in a patient
with senile dementia is due to selective and irreversible
deficiency in the cholinergic functions in the brain.[45] A
number of neurotransmitter receptors and growth factors
appear to influence the synaptic plasticity and memory
through these molecular pathways.[46] The NMDA-type
glutamate receptor has been shown to be important in
hippocampal LTP because of its role as a coincidence
detector that opens its channel when pre- and
postsynaptic neurons fire together.[47] The large amount
of calcium entering through its channel activates CaMKII
via phosphorylation, which in turn phosphorylates AMPA
receptors and increases their number in the postsynaptic
membrane. A change in the number and activity of AMPA
receptors in synapses is thought to be an important
mechanism for the up- or downregulation of synaptic
function in LTP or LTD. Several other neurotransmitter
receptors including metabotropic glutamate, muscarinic
cholinergic, serotonin, dopamine, and adrenergic
receptors are coupled to Mitogen-activated protein
kinase (MAPK) activation through protein kinase A
(PKA) or PKC. Linkages between these receptor
pathways and the MAPK cascade and transcriptional
activation may be responsible for the effects of
commonly prescribed drugs on cognition.[46] For
example, anticholinergic or glutamate-blocking drugs
can impair memory, whereas stimulants or
antidepressants that enhance the effects of serotonin,
dopamine, or norepinephrine can enhance cognition.
Growth factors such as Brain-derived neurotrophic factor
(BDNF) and nerve growth factor, acting through receptor
tyrosine kinase receptors, also stimulate synaptic plasticity
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Gupta and Kulshreshtha: Memory impairment with reference to Alzheimer’s disease
through several mechanisms, including the activation of the
MAPK cascade.[48]
GENERAL MECHANISM OF MEMORY IMPAIRMENT
This impairment of memory is correlated with the
loss of basal forebrain cholinergic neurons. The role of
these neurons in learning and memory is well known, and
its pharmacological blockage leads to the impairment of
learning and memory. Scopolamine-induced amnesic
animal models are used to screen for agents that are
claimed to have cognition-enhancing activity through
the stimulation of the cholinergic system, thus making
them candidates for the treatment of AD.[49] Geriatric
diseases refer to cerebral or spinal disorders caused
by abnormal neuronal death and are accompanied by
impaired cognitive, walking, and motor abilities. The
lack of acetylcholine due to the reduction of
hippocampal cholinergic neuronal activity is one of the
most important causes of memory impairment.
Further, although there are many choline acetyl
transferase agonists and AChE inhibitors for memory
enhancement, they are ineffective and controversial
due to their serious side effects and toxicity. For this
reason, research has tried to identify memory
enhancers from natural materials. Scopolamine is a
muscarinic receptor antagonist that is frequently used in
memory-impaired animals. It inhibits connections
between acetylcholine and muscarinic receptors,
thereby temporarily blocking information transmission
and causing learning and memory impairment.[50]
DRUG DELIVERY, TARGETING, AND THE BLOOD–BRAIN
BARRIER
For the desired CNS effect to be achieved, a systematically
administered compound must pass through the capillary
endothelium of the blood–brain barrier (BBB). Invasive
strategies may circumvent the BBB through neurosurgical
approaches to implant cells, tissues, or drug delivery systems.
Pharmacologically based strategies are being developed to
deliver drugs, polymers, or liposomes to their CNS targets,
and innovative physiologic-based approaches make use of the
Table 4: Allopathic treatment of AD
Generic Brand Approved for
Donepezil Aricept All stages
Galantamine Razadyne Mild to moderate
Memantine Namenda Moderate to severe
Rivastigmine Exelon Mild to moderate
Memantine + donepezil Namzaric Moderate to severe
International Journal of Nutrition, Pharmacology, Neurological Diseases ¦ Volume 7 ¦ Issue 3 ¦ July-September 2017
intrinsic pathway of the carrier-mediated transport of
nutrients (for example, levodopa via the neutral amino acid
transport system) or receptor-mediated transport of peptides,
for example, insulin and transferring.[51]
MEDICATIONS
(1) Allopathic medication for the treatment of memory
impairment.
Types of drugs: The U.S. Food and Drug
Administration has approved the following two types
of medications: cholinesterase inhibitors (Aricept,
Exelon, Razadyne, and Cognex) and memantine
(Namenda)—to treat the cognitive symptoms
(memory loss, confusion, and problems with thinking
and reasoning) of AD. The treatment of memory loss is
illustrated in Table 4.[52]
(2) Ayurveda medication for the treatment of memory
impairment.
The mode of action and herbs to magnify memory are
listed in Table 5.[53-63]
(3) Natural brain chemicals.
Docosahexaenoic acid (DHA): DHA is a major omega-
3 fatty acid of the brain that is necessary for good brain
function. The brains of 42 modern mammalian species
were studied, and they were found to be similar in brain
chemistry, particularly in the predominant use of DHA
in the membrane-rich neural tissues at synapses and in
the retina. It is found mainly in oily fish. DHA is
particularly important for mental performance and
has an important role in the development of the brain
during fetal development and infancy. It is, therefore,
essential that pregnant women either have a regular
dietary source of these omega-3 fats or supplement
them.[64]
Pyroglutamate: N-terminal-truncated A derivatives,
especially the forms having pyroglutamate at the 3rd
position (ApE3) or at the 11th position (ApE11), have
become the topic of considerable study. The master of
communication that has a key brain chemical in
enhancing memory and mental function is the amino
acid pyroglutamate and its derivatives, which are highly
concentrated in the human brain and spinal fluid. It
Side effects
Nausea, vomiting, loss of appetite, and increased frequency
of bowel movements
Nausea, vomiting, loss of appetite, and increased frequency
of bowel movements
Headache, constipation, confusion, and dizziness
Nausea, vomiting, loss of appetite, and increased frequency
of bowel movements
Headache, diarrhea, dizziness, loss of appetite, vomiting,
nausea, and bruising
51
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Gupta and Kulshreshtha: Memory impairment with reference to Alzheimer’s disease

Table 5: The plants that can induce with learning and memory activities
Plant/part used
Curcuma longa
(Zingiberaceae)/leaves
Moringa oleifera
(Moringaceae)/leaves
Acorous calamus
(Scrophulariaceae)/Rhizome
Bacopa monniera
(Scrophulariaceae)/whole
plant
Celastrus paniculatus
(Celastraceae)
Albizzia lebbeck
(Fabaceae)/leaves
Eclipta alba
(Asteraceae)/whole plant
Ficus religiosa (Moraceae)
Pueraria tuberosa
(Fabaceae)/whole plant
Rubia cordifolia
(Rubiaceae)/roots
GABA, Gamma-aminobutyric acid.
Models used Mechanism/result
Morris water maze (MWM), Inhibiting the levels of cholinesterase concentration of enzyme and
and elevated plus maze (EPM) increasing the concentration of acetylcholine
Passive avoidance paradigm (PA) Unknown
and EPM
EPM, Y-maze, and MWM Extract showed potentiality against scopolamine-induced
Alzheimer’s by regulating AchE activity
T-maze test and PA Increased capacity of memory retention in extract-treated rats
EPM and sodium nitrite-induced amnesia Extract had dose-dependent cholinergic activity, thereby
improving memory performance
PA and EPM Brain concentrations of GABA and dopamine were
decreased, whereas the 5-HT level was increased
Extract showed nootropic property and also had the
property of attenuating stress-induced alterations
PA and EPM Extract had antiamnesic activity against scopolamine-induced
amnesia in a dose-dependent manner
EPM, scopolamine-induced amnesia (SIA), Plant extracts elicited significant nootropic effect
diazepam-induced amnesia, etc. in mice and rats by interacting with cholinergic, gabanergic,
adrenergic, and serotonergic systems
SIA Antagonized scopolamine-induced learning and
memory impairment

2. Nowinski WL. Introduction to brain anatomy. In: Miller K, editor.

improves learning, memory, concentration, and the
speed of reflexes.[65]
CONCLUSION
Healthcare awareness contributes significantly to the longer
and stress-free lives of people. A complete knowledge about
noncommunicable diseases including dementia plays an
important role in prolonging the life of human beings.
Prevalence indicates that the number of people with
dementia will continue to grow, particularly among the
elderly. Such investigations in India could better signal the
true state of dementia burden, help plan for future healthcare
needs, and also offer neurobiological problems that impact
fundamental lifestyle and environmental risk factors/
protective factors for AD. Researchers continue to search
for different ways to treat AD and dementias. Currently, there
are many therapies and pharmacologic treatments that
directly concentrate to stop the brain cell death associated
with AD.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
REFERENCES
1. Lagasse P. Nervous System. Columbia Encyclopedia. Columbia
University. 6th ed. New York: Columbia University Press;
2016.
Biomechanics of the Brain. Singapore: Springer Publisher; 2011. p.
228.
3. Marieb N. Brain anatomy. Advanced Human Anatomy and Physiology.
In: Hoehn K, editor. Library of Congress Cataloging-in-Publication
Data. 9th ed. United States: Western Organ University; 2013. p. 201.
4. Sarahroodi S, Esmaeili S, Mikaili P, Hemmati Z, Yousof Saberi Y. The
effects of green Ocimum basilicum hydroalcoholic extract on retention
and retrieval of memory in mice. Anc Sci Life 2012;31:185-9.
5. Sau S, Handral M. Evaluation of memory enhancing activity of leaf
extract of Dalbergia sissoo in mice. Int J Pharm Sci Drug Res
2015;7:263-9.
6. Chakravarthi KK, Avadhani R. Beneficial effect of aqueous root
extract of Glycyrrhiza glabra on learning and memory using
different behavioral models: An experimental study. J Nat Sci Biol
Med 2013;4:420-5.
7. Johnston MV, Alemi L, Harum KH. Learning, memory and
transcription factors. Int Pediatr Res Found 2003;53:369-74.
8. Wixted JT. On common ground: Jost’s (1897) law of forgetting and
Ribot’s (1881) law of retrograde amnesia. Psychol Rev 2004;111:864-79.
9. Dan LL, Anthony SF, Dennis LK, Stephen LH, Larry JJ, Joseph L.
Harrison’s principles of internal medicine. In: William WS, Bruce LM,
editors. Dementia. 18th ed., USA: McGraw Hill Publication; 2012. p. 3300.
10. Raut SB, Parekar RR, Jadhav KS, Marathe PA, Rege NN. Effect of
Jyotis.matı̄ seed oil on spatial and fear memory using scopolamine
induced amnesia in mice. Anc Sci Life 2015;3;130-3.
11. Robertson H, Pryor R. Memory and cognitive effects of ECT:
Informing and assessing patients. Adv Psychiatr Treat 2006;12:228-37.
12. Singhal AK, Naithani V, Bangar OP. Medicinal plants with a potential
to treat Alzheimer and associated symptoms. Int J Nutr Pharmacol
Neurol Dis 2010;2:84-91.
13. Palmer K, Wang HX, Bäckman L, Winblad B, Fratiglioni L.
Differential evolution of cognitive impairment in nondemented
older persons: Results from the kungsholmen project. Am J
Psychiatry 2002;159:436-42.
14. Shahidi S, Setareye S, Mahmoodi M. Effect of Prunusdo mestica
(microbelle) on learning and memory in mice. Anc Sci Life
2013;32:139-43.

52 International Journal of Nutrition, Pharmacology, Neurological Diseases ¦ Volume 7 ¦ Issue 3 ¦ July-September 2017
[Downloaded free from http://www.ijnpnd.com on Monday, March 12, 2018, IP: 103.59.213.150]
Gupta and Kulshreshtha: Memory impairment with reference to Alzheimer’s disease
15. Kumar R, Kumar VR, Kumar VP, Kumar V, Swaminaidu VP. A review
on amnesia. Int J Allied Med Sci Clin Res 2013;1:34-7.
16. Squire LR, Alvarez P. Retrograde amnesia and memory consolidation a
neurobiological perspective. Curr Opin Neurobiol 1995;5:169-77.
17. Andrew DJ, Baig A, Bhanot P, Smolik SM, Henderson KD. The
Drosophila dCREB-A gene is required for dorsal/ventral patterning
of the larval cuticle. Development 1997;124:181-93.
18. Simmons-Mackie N, Raymer A, Armstrong E, Holland A, Cherney
LR. Communication partner training in aphasia: A systematic review.
Arch Phys Med Rehabil 2010;91:1814-37.
19. Mesulam MM, Wieneke C, Hurley R, Rademaker A, Thompson CK,
Weintraub S, et al. Words and objects at the tip of the left temporal lobe
in primary progressive aphasia. Brain 2013;136:601-18.
20. Crosson B, McGregor K, Gopinath KS, Conway TW, Benjamin M, Chang
YL, et al. Functional MRI on languages in aphasia: A review on literature
and methodological changes. Neuropsychol Rev 2007;17:157-77.
21. Buttler C. Syndromes of transient amnesia. Adv Clin Neurosci Rehabil
2006;6:13-4.
22. Chohen L, Benoit N, Van Eeckhout P, Ducarne B, Brunet P. Pure
progressive aphema. J Neural Neurosurg Psychiatry 1993;56:923-4.
23. Singhal AK, Naithani V, Bangar OP. Medicinal plants with a potential
to treat Alzheimer and associated symptoms. Int J Nutr Pharmacol
Neurol Dis 2012;2:84-91.
24. Available from: http://www.nutritionbyangelique.net/2016/05/preventing-
alzheimers. [Last accessed on 2017 Apr 26].
25. Ellison JM. A 60-year-old woman with mild memory impairment.
JAMA 2008;300:1566-74.
26. Rang HP, Dale MM, Ritter JM, Flower RJ, Henderson G. Pathogenesis
of Alzheimer’s Disease. 7th ed. Toronto: Elsevier, Churchill
Livingstone; 2012. p. 481-3.
27. Derecki NC, Cardani AN, Yang CH, Quinnines KM, Crihfield A,
Lynch KR, et al. Regulation of learning and memory by meaningful
immunity: A key role for IL-4. J Exp Med 2010;207:1067-80.
28. Pike J, Bogich T, Elwood S, Finnoff DC, Daszak P. Economic
optimization of a global strategy to address the pandemic threat.
Proc Natl Acad Sci U S A 2014;111:18519-23.
29. Available from: http://www.fda.gov/ForConsumers/ConsumerUpdates/
ucm212747.htm. [Last accessed on 2017 Apr 26].
30. Malve HO, Raut SB, Marathe PA, Rege NN. Effect of combination of
Phyllanthus emblica, Tinospora cardifolia and Ocimum sanctum on
spatial learning and memory in rats. J Ayurveda Integr Med
2014;5:209-15.
31. Shiksharthi AR, Mittal S, Ramana J. Systematic review of herbals as
potential memory enhancers. Int J Res Pharm Biomed Sci 2011;2:918-25.
32. Rubio J, Qiong W, Liu X, Jiang Z, Dang H, Chen SL, et al. Aqueous
extract of Black Maca (Lipidium meyenii) on memory impairment
induced by ovariectomy in mice. Evid Based Complement Alternat
Med 2011;2011:253958.
33. Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M,
et al. Global prevalence of dementia: A Delphi consensus study. Lancet
2005;366:2112-7.
34. Wimo A. The magnitude of dementia occurrence in the world.
Alzheimer Dis Assoc Discord 2003;17:63-7.
35. Qui C, Kivipelto M, von Strauss E. Epidemiology of Alzheimer
disease: Occurrence, determinants, and strategies toward
intervention. Dialogues Clin Neurosci 2009;11:111-28.
36. Eckert GP. Traditional used plant against cognitive decline and
Alzheimer disease. Front Pharmacol 2010;1:138.
37. Kipps CM, Hodges JR. Cognitive assessment for clinicians. J Neural
Neurosurg Psychiatry 2005;76:22-30.
38. Hofer H, Singer B, Williams DR. Different sensations from cones with
the same photopigment. J Vis 2005;5:444-54.
39. Malenka RC. Synaptic plasticity and AMPA receptor trafficking. Ann
NY Acad Sci 2003;1003:1-11.
40. Kandel ER. The molecular biology of memory storage: A dialogue
between genes and synapses. Science 2001;294:1030-8.
41. Squire LR. Memory systems of the brain: A brief history and current
perspective. Neurobiol Learn Mem 2004;82:171-7.
International Journal of Nutrition, Pharmacology, Neurological Diseases ¦ Volume 7 ¦ Issue 3 ¦ July-September 2017
42. Cristina MA. Transcription factors in long-term memory and synaptic
plasticity. Physiol Rev 2009;89:121-45.
43. Johnston MV, Alemi L, Harum KH. Learning, memory and
transcription factors. Int Pediatr Res Found 2003;53:367-74.
44. Webster SJ, Bachstetter AD, Nelson PT, Schmitt FA, Van Eldik LJ.
Using mice to model Alzheimer’s dementia: An overview of the
clinical disease and the preclinical behavioral changes in 10 mouse
model. Front Gene 2014;5:23.
45. Attrey DP, Singh AK, Naved T, Roy B. Effect of seabuckthorn extract
on scopolamine induced cognitive impairment. Indian J Exp Biol
2012;50:690-5.
46. Roberson ED, English JD, Adams JP, Selcher JC, Kondrastick C,
Sweatt JD. The mitogen activated protein kinase couple binding protein
phosphorylation. J Neurosci 1999;19:4337-48.
47. Penn AA, Riguelman PA, Feller MB, Shatz CJ. Competition in
retinogeniculate patterning driven by spontaneous activity. Science
1998;279:2108-12.
48. Ying SW, Futter M, Rosenblum K, Webber MJ, Hunt SP, Bliss TV, et al.
Brain derived neurotrophic factor induces long term potentiation in intact
adult hippocampus: Requirement for ERK activation coupled to CREB and
upregulation of Arc synthesis. J Neurosci 2002;22:1532-40.
49. Soodi M, Naghdi N, Hajimehdipoor H, Choopani S, Sahraei E.
Memory-improving activity of Melissa officinalis extract in naïve
and scopolamine-treated rats. Res Pharm Sci 2014;9:107-14.
50. Choi YJ, Yang HS, Jo JH, Lee SC, Park TY, Choi BS, et al. Anti-
amnesic effect of fermented ganodermalucidum water extracts by lactic
acid bacteria on scopolamine-induced memory impairment in rats. Prev
Nutr Food Sci 2015;20:126-32.
51. Pardridge WM. The blood brain barrier: Bottleneck in brain drug
development. NeuroRx 2005;2:3-14.
52. Available from: http://www.alz.org/alzheimers_disease_standard_
prescriptions.asp. [Last accessed on 2017 Apr 26].
53. Sullivan CP, Berg EA, Elliott-Bryant R, Fishman JB, McKee AC,
Morin PJ, et al. Pyroglutamate-A 3 and 11 colocalize in amyloid
plaques in Alzheimer’s disease cerebral cortex with pyroglutamate-
A11 forming the central core. Neurosci Lett 2011;505:109-12.
54. Nayana R, Chandrashekar M, Sultanpur VS. Evaluation of nootropic
activity of Curcuma longa leaves in diazepam and scopolamine-induced
amnesic mice and rats. Int J Basic Clin Pharmacol 2015;4:714-9.
55. Mohan M, Kaul N, Punekar A, Girnar R, Junnare P, Patil L. Nootropic
activity of Moringa oleifera leaves. J Nat Remedies 2005;5:59-62.
56. Valay S, Ragavendra M, Sushma M, Rao UM. Evaluation of nootropic
activity of Acorous calamus against scopolamine induced Alzheimer’s.
World J Pharm Pharm Sci 2015;4:1743-58.
57. Vollala VR, Upadhya S, Nayak S. Learning and memory-enhancing
effect of Bacopa monniera in neonatal rats. Bratisl Lek Listy
2011;112:663-9.
58. Bhanumathy M, Harish MS, Shivaprasad HN, Sushma G. Nootropic
activity of Celastrus paniculatus seed. Pharm Biol 2010;48:324-7.
59. Chintawar SD, Somani RS, Kasture VS, Kasture SB. Nootropic activity
of Albizzia lebbeck in mice. J Ethnopharmacol 2002;81:299-305.
60. Thakur VD, Mengi SA. Neuropharmacological profile of Eclipta alba
(Linn.) Hassk. J Ethnopharmacol 2005;102:23-31.
61. Kaur H, Singh D, Singh B, Goel RK. Anti-amnesic effect of Ficus
religiosa in scopolamine-induced anterograde and retrograde amnesia.
Pharm Biol 2010;48:234-40.
62. Rao NV, Pujar B, Nimbal SK, Shantakumar SM, Satyanarayana S.
Nootropic activity of tuber extract of Pueraria tuberosa (Roxb). Indian
J Exp Biol 2008;46:591-8.
63. Patil RA, Jagdale SC, Kasture SB. Antihyperglycemic, antistress and
nootropic activity of roots of Rubia cordifolia Linn. Indian J Exp Biol
2006;44:987-92.
64. Karuna AT, Uma AB, Mandar RZ, Rahul SS. Neuroprotective and
nootropic activity of Clitorea ternatea Linn. (Fabaceae) leaves on
diabetes induced cognitive decline in experimental animals. J Pharm
Biol Allied Sci 2014;6:48-55.
65. Bradbury J. Docosahexaenoic acid (DHA): An ancient nutrient for the
modern human brain. J Nutr 2011;3:529-54.
53