What is Cognitive Decline & Dementia?

Cognitive decline refers to a reduction or worsening in mental functions—such as memory, attention, language, executive function, and visuospatial skills. Normal aging may produce mild, benign age-related changes (like occasional word-finding difficulties) that do not interfere with daily independence. On the other hand, dementia—now termed Major Neurocognitive Disorder by the DSM-5—represents a noticeable drop from a person's previous baseline that is severe enough to interfere with independent activities of daily living (ADLs) and occupational or social functioning. Mild neurocognitive disorder (mild cognitive impairment) is frequently an early precursor, that causes measurable deficits that represent a decline from baseline, but do not yet compromise a person's ability to function.

A sudden change in behavior is not primarily indicative of dementia. New agitation or confusion should prompt evaluation for delirium and reversible causes, such as infection, pain, dehydration, constipation, urinary retention, metabolic abnormalities, or medication effects.

Primary Causes of Cognitive Decline 
 

• Alzheimer’s Disease: The most common form of dementia, presumably caused by toxic amyloid-beta plaques and tau tangles

• Vascular Dementia: caused by conditions that reduce blood flow to the brain

• Lewy Body Dementia (DLB): Characterized by Lewy bodies. Cognitive symptoms and psychiatric manifestations appear within one year of parkinsonian motor symptoms.

• Parkinson’s Disease Dementia (PDD): Occurs when a patient has a diagnosis of Parkinson's disease for more than a year before significant cognitive decline develops and evolves into dementia.

• Frontotemporal Lobar Degeneration (FTLD): Involves progressive atrophy localized to the frontal and temporal lobes, prominently featuring early changes in personality, behavior, or language.

  • Pick's Disease: A classic subtype characterized by severe frontotemporal atrophy and microscopic Pick bodies, presenting with profound early changes in social conduct and empathy while memory is often spared initially.

• Huntington's Disease: A monogenic, autosomal dominant disorder that primarily targets the basal ganglia (striatum) and causes subcortical dementia (executive dysfunction, processing speed deficits) and involuntary chorea movements. 

• Mixed Dementia: Two or more neurodegenerative disorders

Secondary Causes of Cognitive Decline & Mimickers
 

• Metabolic & Endocrine Disorders: Hypothyroidism; severe vitamin deficiencies (Vitamin B12, thiamine/B1 [Wernicke-Korsakoff syndrome], niacin/B3): usually caused by chronic alcohol use, malnutrition, malabsorption disorders; electrolyte disturbances (e.g., severe hyponatremia); and organ failure (hepatic or uremic encephalopathy).

• Infections: Chronic central nervous system infections (neurosyphilis, Lyme disease, fungal meningitis), HIV-associated neurocognitive disorder, and severe systemic infections.

• Neurological & Structural Conditions: Normal pressure hydrocephalus (characterized by the triad of gait disturbance, urinary incontinence, and cognitive impairment), subdural hematomas, and brain tumors.

• Substance- or Medication-Induced Neurocognitive Disorder: from side effects or toxicity (e.g., anticholinergics, sedatives, benzodiazepines, opioids, inhalants, PCP)

• Psychiatric Comorbidities: Severe or treatment-resistant depression (pseudodementia of depression) and chronic anxiety.

• Delirium: An acute, fluctuating disturbance in attention and awareness typically triggered by an acute medical illness, surgery, being in the hospital, or having severe pain. It has a rapid onset and distinct alteration of consciousness, unlike progressive dementia.

• Sensory Impairment: Uncorrected, severe vision or hearing loss leading to social withdrawal, misinterpretation of environmental cues, and poor cognitive screening test performance.

How is it Diagnosed?

History & Physical, including screening tools like the mini-mental state exam 
 

Labs: TSH, B12, CMP, HIV and Syphilis serology
 

Advanced Testing: Cerebrospinal fluid (CSF), blood tests, and amyloid PET scan when indicated. They are highly accurate in ruling out Alzheimer's Disease. 
 

Imaging (MRI / CT) *CT often not as sensitive
 

• • Disproportionate hippocampal atrophy and temporoparietal cortical thinning: Suggests Alzheimer's Disease

  • Periventricular white matter hyperintensities and lacunar infarcts: Indicates ischemic white matter disease and subcortical ischemic vascular dementia (characterized by gradual onset of slow processing, executive dysfunction, gait instability, and urinary incontinence).

  • Multiple cortical/subcortical strokes: Suggests Multi-Infarct Dementia (MID) or Post-Stroke Dementia.

  • Disproportionate frontal and/or temporal lobe atrophy (with spared posterior regions): Suggests Frontotemporal Lobar Degeneration (FTLD).

  • Marked ventriculomegaly disproportionate to sulcal widening: Suggests Normal Pressure Hydrocephalus (NPH).

  • Crescent-shaped extra-axial collection shifting midline structures: Suggests Subdural Hematoma (often post-traumatic in older adults).

Management
 

General Nonpharmacological Management
 

• Consistent routine (shower, meds, meals, activities) to reduce confusion and anxiety.

• Maintain a calm and clean home environment. Encourage daytime light exposure. 

• Look for pain, hunger, thirst, constipation, urinary retention, infection, fatigue, loneliness, overstimulation, or medication effects when behavior suddenly changes.

• Speak slowly and calmly, use simple sentences and one-step instructions, offer limited choices, avoid arguing or repeatedly correcting the person, and redirect when they become distressed.

• Regular physical sctivity can improve mobility, sleep, mood, restlessness, and overall function.

• Music, gardening, crafts, and pets can provide stimulation and reduce boredom or agitation.

• Regular interaction with family and friends can reduce isolation and provide cognitive stimulation.

• Orientation & Memory Aids: Clocks, calendars, labels, photographs, written reminders

• Wandering Safety: Door alarms, identification bracelets, secured hazardous areas, supervision, and other environmental safeguards can reduce injury or elopement risk.

• Sensory Optimization: Correct hearing and vision impairment when possible and ensure hearing aids and glasses are available
   

Behavioral & Psychological Symptoms

Treatment begins by identifying potentially reversible triggers such as pain, infection, medication effects, constipation, sleep disruption, or environmental stress. Behavioral and environmental interventions are generally preferred first. SSRIs, such as sertraline, may be considered for depression, anxiety, irritability, or some forms of agitation. Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and memantine, primarily used to treat cognitive symptoms, may also improve certain behavioral or neuropsychiatric symptoms in some patients. For severe agitation, aggression, hallucinations, or delusions causing substantial distress or danger, additional medication may be considered. Antipsychotics require particular caution because their use in older adults with dementia is associated with increased risks, including cerebrovascular events and mortality. Two atypical antipsychotics include Rexulti and Nuplazid. Brexpiprazole (Rexulti) is FDA-approved for agitation associated with dementia due to Alzheimer's. Pimavanserin (Nuplazid) is FDA-approved for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis, with or without dementia. Dextromethorphan/bupropion (Auvelity) is also FDA-approved and is a non-antipsychotic treatment option for agitation associated with Alzheimer's dementia.​​

Cognitive Medications - they do not cure dementia or stop the underlying neurodegenerative disease
 

• Cholinesterase Inhibitors (donepezil, rivastigmine, galantamine): cognition enhancer

  • Mechanism: Prevent the breakdown of acetylcholine, enhancing cholinergic neurotransmission.

  • Indications: Mild to severe Alzheimer's disease and Lewy body dementia.

  • Side Effects: Gastrointestinal distress (nausea, diarrhea, weight loss), bradycardia, and vivid dreams.
     

• NMDA Receptor Antagonist (memantine): cognition enhancer

  • Mechanism: Regulates glutamate activity to prevent excitotoxic neuronal damage.

  • Indications: Moderate to severe Alzheimer's disease (alone or with a cholinesterase inhibitor).

  • Side Effects: Dizziness, headache, confusion, and constipation
     

​