What is the evaluation and management approach for an adult with recent difficulty finding words, inability to recall birthplace and time, who is stable, well-oriented, but experiencing anxiety and depression?

Evaluation and Management of Recent-Onset Word-Finding Difficulty with Memory Concerns

This patient requires immediate comprehensive cognitive evaluation including validated cognitive testing (MoCA or Mini-Cog), complete laboratory workup, and brain MRI to differentiate between progressive aphasic syndrome (likely Alzheimer's disease), depression-related cognitive symptoms, or other reversible causes. 1, 2

Initial Clinical Assessment

Characterize the Cognitive Symptoms Precisely

• Ask for specific examples of word-finding difficulties rather than accepting general descriptions, as "memory loss" means different things to patients versus clinicians 2
• Determine if the patient has anomia (difficulty naming objects), agrammatism, speech sound errors, or impaired comprehension, as these distinguish progressive aphasic syndromes from other causes 1
• Inquire about difficulties with learning and recalling newly acquired information and recent life events (episodic memory), which suggests progressive amnesic syndrome 2
• Document onset timing, progression pattern, and functional impact on work, daily activities, and safety 2, 3

Critical Distinction: Depression vs. Neurodegenerative Disease

The presence of anxiety and depression does NOT exclude—and may actually herald—early Alzheimer's disease or related disorders. 1, 2

• More than half of patients who subsequently develop dementia had depression or irritability symptoms before cognitive impairment became apparent, indicating mood changes are often early manifestations of neurodegenerative disease 2
• Depression-related cognitive complaints typically involve decreased motivation but retained ability when prompted, whereas neurodegenerative disease shows true inability despite effort 2
• Both conditions frequently coexist (up to 85% of depressed patients have significant anxiety; up to 90% of anxiety disorder patients develop depression), making this a particularly high-risk presentation 4, 5

Obtain Collateral History

• Interview a family member or close contact separately to identify discrepancies between patient self-report and observed functioning, as diminished insight is common in cognitive impairment 2, 3
• Ask the informant about specific examples of memory lapses, word-finding difficulties, and changes in daily functioning they have directly observed 2

Mandatory Diagnostic Workup

Cognitive Testing

Administer a validated brief cognitive screening tool immediately rather than relying on subjective reports or clinical impression alone 2, 3:

• Montreal Cognitive Assessment (MoCA) or Mini-Cog 2, 3
• Do not use geriatric screening tools if patient is younger, as age-appropriate instruments are required 6

Laboratory Evaluation (Tier 1 - All Patients)

Order the following tests to identify reversible causes 2, 3:

• Complete blood count (screens for anemia, infection) 3
• Comprehensive metabolic panel (electrolytes, renal function, glucose, hepatic function) 3
• Thyroid-stimulating hormone (TSH) with free T4 if abnormal 3
• Vitamin B12 and folate levels 3
• Hemoglobin A1c (diabetes control) 3
• Liver function tests (ALT, AST for hepatic encephalopathy) 3

Neuroimaging

Brain MRI (non-contrast) is mandatory to evaluate structural causes and characterize atrophy patterns 2, 3:

• MRI is superior to CT for detecting vascular lesions, hippocampal atrophy, white matter disease, and subtle structural abnormalities 3
• 3T MRI is preferred over 1.5T if available and no contraindications exist 3
• MRI will identify stroke, white matter hyperintensities, atrophy patterns (hippocampal, posterior cortical), hydrocephalus, space-occupying lesions, and inflammatory/infectious processes 3

Syndromic Diagnosis Based on Clinical Features

Progressive Aphasic Syndrome (Most Likely Given Word-Finding Difficulty)

Word-finding difficulty as a prominent early feature suggests progressive aphasic syndrome 1:

• Logopenic variant primary progressive aphasia (PPA) is usually due to Alzheimer's disease and presents with anomia and impaired repetition due to auditory-verbal working memory impairment 1
• Semantic variant PPA (impaired comprehension, loss of word meaning) is usually due to frontotemporal lobar degeneration 1
• Non-fluent variant PPA (agrammatism, speech sound errors) is usually due to frontotemporal lobar degeneration-tau 1

Progressive Amnesic Syndrome (If Memory Predominates)

Difficulty learning and remembering new information, often accompanied by executive dysfunction, depression, and anxiety 1:

• Usually Alzheimer's disease, often with co-pathologies (AD + vascular cognitive impairment, AD + Lewy body disease) 1
• Depression and anxiety are common early features of progressive amnesic syndrome 1

Management Algorithm

Step 1: Treat Depression and Anxiety While Pursuing Diagnostic Workup

Do not delay dementia workup while treating depression, as both conditions frequently coexist 2:

• Initiate SSRI therapy for depression and anxiety (venlafaxine has demonstrated efficacy for both depression and generalized anxiety disorder) 4, 5
• Reassess cognition after 8-12 weeks of adequate antidepressant treatment 2
• If cognitive deficits persist despite mood improvement, this strongly suggests underlying neurodegenerative disease 2

Step 2: Proceed to Formal Neuropsychological Testing

If screening tests suggest impairment, proceed to comprehensive neuropsychological assessment focusing on attention, memory, language, and executive function domains 3:

• Formal testing objectively characterizes cognitive deficits and establishes baseline functioning for longitudinal monitoring 3, 6
• Attention lapses are strongly correlated with memory failures and should be systematically evaluated 3

Step 3: Consider Advanced Biomarker Testing (Selected Cases)

For patients with persistent cognitive impairment after initial workup 3:

• CSF Alzheimer's biomarkers (Aβ42/Aβ40 ratio, p-tau181, t-tau) identify or exclude AD as the underlying cause 3
• Blood biomarkers for amyloid pathology are emerging tools that may reduce need for CSF or PET imaging 3

Step 4: Refer to Neurology or Dementia Specialist

Refer when diagnostic uncertainty persists after initial evaluation or when atypical presentations occur 2:

• Early-onset cognitive impairment (age <65) has higher likelihood of atypical or non-Alzheimer's pathology 3
• Progressive aphasic syndromes require specialized evaluation to determine variant and underlying pathology 1

Step 5: Longitudinal Follow-Up

Schedule reassessment every 6-12 months using the same cognitive instruments to track trajectory 2:

• Progressive decline on serial testing strongly favors neurodegenerative disease over primary depression 2
• Monitor for emergence of additional cognitive, behavioral, or motor symptoms that refine syndromic diagnosis 1

Critical Pitfalls to Avoid

• Do not attribute cognitive symptoms solely to depression or anxiety without thorough evaluation, as mood symptoms are often early manifestations of neurodegenerative disease 2
• Do not dismiss subjective forgetfulness as "normal aging" without objective assessment, as changes warrant diagnostic evaluation 3
• Do not focus exclusively on memory; assess other cognitive domains including executive function, language, and visuospatial abilities 2
• Do not assume the patient is well-oriented based on superficial assessment, as patients with cognitive impairment often have diminished insight into their condition 2, 3
• Beware of diagnostic overshadowing where features of underlying neurological illness are attributed to psychiatric conditions 1

Pharmacologic Considerations (If Alzheimer's Disease Confirmed)

Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are FDA-approved for mild to moderate Alzheimer's disease 7:

• Donepezil has demonstrated efficacy in severe Alzheimer's disease at doses of 10 mg/day and 23 mg/day 7
• Memantine can be added for moderate to severe disease 7
• Treatment should be initiated early once diagnosis is established, as benefits are greatest in earlier stages 7