The Female: Male ratio of early onset Dementia is 2:1. About 10 % of population over 65 years and between 25 and 40 % over 85 years have Alzheimer’s disease. The condition generally lasts 7-15 years. HIV Associated dementia is found in 15 % of patients with advanced HIV disease. Alzheimer's Dementia (AD) constitutes a significant worldwide medical, social, and financial burden. The World Alzheimer Report 2022 indicated that over 55 million individuals globally suffer from AD or illnesses connected to it, over 60% of whom reside in low-and middle-income countries .Thiscountries. This figure is expected to rise to 82 million by 2030 and 138 million by 2050. In Nigeria, there is a problem with access to health care, lack of awareness by the lay public on preventive strategies for Dementia and lack public support for health care.

1. Trauma: is an independent risk factor but perhaps only in those with a genetic predisposition
2. Genetic: a family history of Alzheimer’s disease increases the risk of the disease four-fold. A familial form is inherited as an autosomal dominant trait
3. Molecular genetics:
4. Mutations in the chromosome 14 locus - most early-onset, familial Alzheimer’s disease
5. The apolipoprotein e gene on chromosome 19 has been implicated in late-onset Alzheimer’s disease; the genotype e4-e4 confers a higher risk
6. Chromosome 21 (Down’s syndrome) have a high risk of early-onset Alzheimer’s disease - the gene for b-amyloid precursor protein is found on chromosome 21.

1. Older age (≥65 years)
2. Systemic hypertension
3. Diabetes
4. Obesity
5. Smoking
6. Alcohol use disorder
7. Physical inactivity/sedentary lifestyle
8. Social isolation/loneliness
9. Emotional illness e.g Depression

1. Diminution of the cortex and subcortical white matter volume, with dilatation of the cortical spaces and enlargement of the lateral ventricles
2. Loss of cortical neurons: particularly in outer 3 layers of cortex, but all layers affected. Hippocampus, parietal regions, and nucleus basalis of Meynert usually affected first; and visuosensory and sensorimotor areas relatively spared until later
3. Amyloid plaques: are the critical pathological feature of Alzheimer’s disease - the plaques consist of amyloid peptide b-A4. The extent correlates with severity
4. Neurofibrillary tangles: abnormal phosphorylation of ‘tau’ proteins implicated in AD – e.g. A68 protein (Alzheimer disease associated protein – ADAP). The degree of cognitive impairment correlates with the number of neurofibrillary tangles
5. Glial proliferation and Granulovascular degeneration: especially in the hippocampus.

1. Cholinergic loss: substantial depletion of choline acetyltransferase (CHAT) and acetylcholine esterase is found, mainly in the temporal cortex.
2. Noradrenergic loss: reduced noradrenaline concentrations in the cortex and hippocampus. Cell loss in locus coeruleus, especially in early onset AD.
3. Serotonergic loss: loss of cortical 5-HT₂ receptors – especially in frontal and temporal lobes. Cell loss and neurofibrillary tangles in nucleus raphe dorsalis.
4. b-A4 amyloid may be neurotoxic, possibly altering calcium homeostasis and thereby altering neuronal susceptibility to the effects of excitotoxins such as glutamate.
5. Other neurotransmitters: decreased somatostatin, decreased GABA, decreased CK, deficiency of mitochondrial alpha ketoglutarate dehydrogenase complex.

Dementia symptoms and signs are progressive and  varies greatly from different individual depending on the underlying causes, other health conditions and the individual’s cognitive functioning prior to onset of illness

1. Cognitive: Memory loss (STM > LTM), problems of language, praxis, and gnosis become increasingly apparent as the disease progresses.
2. Functional: inability to perform at normal level in everyday decision making

1. Neurological: Perceptible delay in word finding, Speech can be hesitant, Extrapyramidal features often emerge with the appearance of primitive reflexes and sometimes myoclonus
2. Biological and Psychological symptoms of Dementia (BPSD):
   1. Apathy exists in about 50% of cases in early and intermediate stages
   2. Depressive symptoms in 40-50% of dementia, but diagnosis occurs in 10-20%
   3. Psychosis includes delusion, hallucination, wandering, and misidentification.
   4. Others: Personality changes, Anxiety, Nighttime disturbance, Appetite change.

1. Mild dementia: The person notices deterioration in memory, particularly for recent events. May also find it difficult to concentrate, think flexibly, plan, and take decisions. They are likely to feel bewildered, anxious and sad. They may become angry and defensive when others point out errors.
2. Moderate dementia: The person has severe memory problems. Only early memories are retained. Recent events are not remembered, or rapidly forgotten. They may not know the day, date or time of day. They often do not know where they are. They cannot communicate clearly, having problems finding the right word and using the wrong words.
3. Severe dementia: The person has complete memory loss. They may no longer recognize their close family. They have severe speech difficulties or are unable to communicate. They may be apathetic and totally inactive, but at times can be agitated and verbally and physically aggressive. They cannot coordinate their physical movements; may have lost the ability to walk and feed themselves and have difficulty swallowing. They are likely to be incontinent of urine and feaces.

1. CT: temporal lobe volume is reduced. serial scanning shows progressive volume loss.
2. SPECT: symmetrical reduction in grey matter perfusion, correlates with the severity
3. PET: bilateral reduction of oxygen use and glucose uptake, initially in temporal lobes.
4. EEG: slowing of the dominant a Also, appearance of q and d activity
5. Psychometry: delayed recall is the best overall discriminator for early disease

There is no cure for dementia. The goal is to support the persons living with the illness and their caregivers and manage their symptoms using different interventions.

1. Pharmacological:
2. Drugs that treat cognitive symptoms
3. Cholinesterase inhibitors e.g. Donezepil (used to treat all stages of AD), Rivastigmine (mild to moderate AD as well as mild-to-moderate dementia associated with Parkinson’s disease), and Galantamine (used for mild-to moderate stages of AD. They are well tolerated and common side effects include nausea, vomiting, loss of appetite and increased frequency of bowel movement
4. NMDA receptor antagonists (Glutamate regulators) e.g. Memantine, for moderate-to-severe AD and vascular dementia. The side effects include headache, constipation, dizziness and confusion

iii. Cholinesterase inhibitor + Glutamate regulator e.g. Donepezil and Mimantine (Namzaric) used for moderate-to-severe AD.

2023. Drugs that modify disease progression (amyloid-targeting approaches) e.g. Lecanemab and Aducanumab which got FDA approval in 2023. They are anti-amyloid antibody intravenous therapy. It moderately slow cognitive and functional decline in early stage cases of AD and used in MCI. The common side effects of the drugs include flushing, chills, fever, body aches, amyloid-related imaging abnormalities (ARIA) with brain oedema, etc.
2024. Drugs for non-cognitive symptoms (Behavioral and psychological symptoms): nondrug strategies should be the first approach, however when this fails, drugs intervention may be considered.
2025. Atypical antipsychotics e.g. Risperidone for Behavioral and psychological symptoms (sleep disturbances, agitation, hallucinations and delusions), Brexpiprazole is the only FDA approved atypical antipsychotic used in the treatment of agitation due to AD. Antipsychotics are usually used for a short time and should be gradually tapered off once the resolution of behavioral symptoms is observed.
2026. Antidepressants e.g. SSRI are better tolerated for Depressive symptoms

iii. Orexin receptor antagonist e.g. Suvorexant used for insomnia in people with mild-to-moderate AD

1. Manage the underline physical illness like hypertension and diabetes, thyroid diseases

2. Non-pharmacologic: Psychological interventions, Environmental manipulations, Caregiver Psychoeducation, Bright light, White noise, Recreational Activities, Sensory stimulation.

1. Regular exercise
2. Healthy diet
3. avoid smoking and harmful use of alcohol
4. Weight reduction and control
5. Maintain healthy blood pressure, cholesterol and blood sugar levels
6. Try new things to keep your mind ative
7. Spend time with loved ones and engage in community life