Menopause is the permanent cessation of menstruation at the end of the reproductive cycle. The well known symptoms of menopause are Hot flushes, night sweat, palpitation, vaginal dryness, muscle –joint pain and mood swing but many patient may experience Brain Fog or cognitive decline ie problem with memory, concentration, confusion, and problem with thinking and learning. Aging brain is associated with poor cognition (MIC -mild impaired cognition, Delirium and pseudo dementia) dementia and Alzheimer’s disease. Impaired Cognition includes

• Memory issue,
• Confusion,
• Difficulties in focusing
• Decreased attention.

Some cognitive disorder is temporary or reversible and some are permanent or irreversible.

Dementia – are primary, progressive irreversible disease.

Alzheimer’s disease is the most prevalent dementia. Old age and female are risk factors. Genetic cause, cholinergic hypothesis, and brain atrophy are the etiology behind.

In Alzheimer’s disease the brain shrinks and weighs about two-thirds of its original weight and is characterized by 4 A’s.

1. Agnosia: inability to recognize people and objects
2. Aphasia: language disturbance
3. Amentia: inability to learn and recall
4. Apraxia: motor dysfunction.

We often find women with mild cognitive impairment during the menopausal transition with the majority reporting worsening verbal memory. And also suffers from increased risk of mood change and depressive episode. But whether menopause triggers this brain fog or impaired cognition is still a matter of controversy.

Natural menopause is unlikely the sole reason, there are other Risk factors such as

• Busy work,
• Depression,
• Insomnia
• Stressful life events,
• Inadequate social support,
• Multiple role player,
• Elevated body mass index,
• Current smoker status,
• Young age,
• African American,
• Cardiovascular disease
• Hypertension, Diabetes
• Premature Menopause.
• Job stress,
• Anxiety and menopausal symptoms.

Memory problem predominantly a function of stressful life, which again diminished attention and concentration.
multiple burdens resulting in diminished attention and concentration.

Premature ovarian insufficiency or menopause has long-term negative effects on cognitive function and on verbal fluency, usual memory task and decline psychomotor speed. Decline of memory is usually most pronounced within 12 months of final menstruation. Premature Menopause is menopause before 40 years of age, which can be due to variety of causes:

• Surgery (BSO),
• Chemotherapy,
• Radiotherapy,
• Chromosomal or genetic defects
• Spontaneous premature ovarian failure.

In contrast to natural menopause,
Administration of estrogen in POI improves the episodic memory and cognitive function significantly..

MHT in these women is helpful for improving short-term cognitive capacity.

Role of estrogen

Estrogen enhances formation of synapses, neurite growth, hippocampas and precotex neurogenesis. estrogen protects against apoptosis and against neural injury including toxicity induced by excitatory neurotransmitter , amyloid, oxidative stress and ischemia. Fluctuation in estrogen and progesterone level and decline in estrogen level are potentially relevant to cognitive changes occurring during premature menopause.In addition the
menopausal cardinal symptoms, hot flashes, night sweats, sleep disturbance, depression, anxiety, mood swing can leave one feeling more fatigue and indirectly more cognitive impairment.

Exogenous estrogen has been shown to improve the subjective and objective sleep disturbance attributed to a decrease in hot flashes.

The AAN (American Academy of Neurology) identify following criteria for diagnosis of MCI (Mild Cognitive Impairment):

• Memory Complain
• Objective memory impairment
• Normal general thinking and reasoning skill

Ability to perform normal daily activities
For evaluation need thorough history from the patient on family member -medical history (DM, CVS, endocrine, neurology) and drug history. (Analgesics, sedatives,hypnotis,psycotropics,anticholinergics). Labwork needs TSH, CBC,RBS,Prolactin,VDRL, Vit B12 and CT Scan Brain.

Treatment needs to involve multidisciplinary approach, including the participation of Neurologist, Geriatric psychiatrist, and mental health specialists. Life style modification, psychotherapy, pharmacotherapy and combination.

Pharmacotherapy
Estrogen is neurotropic and neuroprotective, affecting serotonergic, cholinergic and dopaminergic systems of brain which are important for cognition and mood. But Estrogen therapy during menopause may not improve cognitive function. Rather if MHT initiated in a elderly women there is increase the risk of dementia.

1. A critical determinant of the effect of estrogen on CNS and CVS appears to be the timing of estrogen exposure in relation to menopausal transition – that is exposure early in the menopausal transition or post-menopausal period confers cognitive benefit, whereas exposure later in the post menopause confers neutral or detrimental effect (Critical Timing Hypothesis or Healthy cell bias hypothesis.)
2. Antidepressant (SSRI & SSNRI)
   Selective serotonin reuptake inhibitor/ selective serotonin nor-epinephrine reuptake inhibitor – May helpful to improve cognition if associated with depression.
3. Acetylcholine esterase inhibitor
   Beneficial for patient with early dementia
4.  SERM

Temoxifen used in Breast cancer prevention and Raloxifene used in osteoporosis prevention. In large clinical trail Reloxifen has no effect onoverall cognitive function, but Tamoxifen might impair cognitive function. Cognitive effects of SERMs are yet to be studied.

Life Style Modification
Sleep and Enough Rest improves cognitive capacity and reduce the level of stress hormone. Mental, activities, recreation tend to improve cognitive capacity. Reading books, singing, gardening, swimming, playing musical instrument, solving puzzles prevent decline in cognition and dementia. Exercise has been shown to prevent the pathology of AD in high-risk women, Meditation helps to relax. Strengthening brain by trying to learn something new for reading, daily keep the brain functioning and young.
Diet low in saturated fats, high in omega-3 and rich in antioxidants, whole egg, and chicken are helpful. Coffee seems to protect the brain against cognitive impairments and boost thinking skill. Orange drink reduces the risk of dementia and 34% reduction in memory loss. Control of DM, Hypertension and menopausal symptoms may be useful in preventing cognitive impairment.

Psychotherapy
Several forms may be helpful including cognitive behavioral therapy (CBT), interpersonal therapy psychodynamic psychotherapy, and life style modification.

Conclusion
.NICE guidelines 2015 focused on the use of HRT for up to 5 years for the symptomatic relief and prevention of chronic diseases. Getting elder and going through menopause does not mean that women will feel old and will have memory problems. Lifestyle modification and Psychotherapy, HRT in special occasion may prevent brain aging. From today we have to take action so that we feel younger not only that also we look younger