Can TMS help early-onset Alzheimer’s disease?
In this single case report, repetitive transcranial magnetic stimulation was followed by marked improvement on repeat cognitive testing. A 44-year-old woman with clinical and laboratory characteristics of definite early-onset Alzheimer’s disease was retested after her 19th rTMS session and scored higher on global cognition, memory, verbal functioning, executive functioning, working memory, and attention. This is a case report published in Clinical Neurophysiology Practice in 2023, not a controlled trial, so it describes what happened to one patient rather than what happens on average.
Non-invasive neuromodulation can enhance neuroplasticity, with the potential to strengthen synaptic activity and activate neuronal populations tied to memory and learning pathways. Several studies have found high-frequency rTMS to be an effective treatment for people with mild cognitive impairment and Alzheimer’s disease when applied to the left and/or right dorsolateral prefrontal cortex, with clear improvements on standardized assessments of cognitive function.
What the data show:
- Memory: Index score 37.2 to 45.4, a 22% gain, moving the z-score from -4.19 to -3.64
- Executive functioning: 32.4% improvement from a baseline index of 77.4 (z = -1.5)
- Verbal functioning: 148% improvement from a baseline index of 25.0, which was five standard deviations below the normative mean
- Working memory: 19% improvement from a baseline index of 62.0 (z = -2.53)
- Attention: 13.2% improvement from a baseline index of 76.4 (z = -1.58)
- Global cognition: Index score 60.8 to 71.8, an 18.1% gain, with the z-score moving from -2.61 to -1.93
The authors describe this as the first known case report applying rTMS to a clinically and laboratory-confirmed patient with early-onset Alzheimer’s disease.
Dr. Kumar’s Take
Early-onset Alzheimer’s disease, defined by signs and symptoms before age 65, leaves clinicians with very little to offer, and the authors are direct about why they went looking: the efficacy of pharmacological treatment for both early and late-onset disease is significantly limited. That is the honest backdrop for a report like this one. What I find clinically interesting is the pattern of the numbers rather than any single one of them. This patient’s verbal functioning sat five standard deviations below the normative mean at baseline, the worst domain she had, and it was also the domain that moved the most. Her global score climbed from more than two and a half standard deviations below average to under two. I would not change practice on one unblinded case, and I do not read this as proof that rTMS treats Alzheimer’s disease. I read it as a reason to keep running the controlled studies.
What the Research Shows
This case report describes a 44-year-old woman who presented for evaluation and management of progressive cognitive decline and poor mood that had become most noticeable two years before she came to the clinic. Her primary symptoms were disorientation, short- and long-term memory loss, misplacing important objects, and deficits in executive function. She had worked as an executive in a large organization for seven years before the onset of symptoms.
Mood disorder was assessed and did not explain the picture. Her PHQ-9 score was 2 and her Burns Depression Inventory score was 3, and she had no impairments in basic activities of daily living. Her vitals, cranial nerves, and neuromuscular exam were normal. On mental status testing she was oriented times four but showed slight bradyphrenia, could not spell “world” in reverse, and had impaired recall: 1 of 3 immediate, and 1 of 3 delayed at 3, 5, and 7 minutes, unchanged when cues were given at all three time points. Her verbal responses were slow and her insight into her own cognitive symptoms appeared impaired.
Cognition was measured with the NeuroTrax computerized testing platform, which has high test-retest reliability and is validated to differentiate cognitively healthy individuals from those with mild cognitive impairment. Scores are standardized by age and education to a mean of 100 with a standard deviation of 15.
Results in Real Numbers
At baseline she scored more than two standard deviations below average on global cognition (60.8, z = -2.61), memory (37.2, z = -4.19), verbal functioning (25.0, z = -5.0), problem-solving (66.5, z = -2.33), and working memory (62.0, z = -2.53). She scored more than one standard deviation below average on executive functioning (77.4, z = -1.5), attention (76.4, z = -1.58), and visual-spatial processing (80.8, z = -1.28).
Testing was repeated after her 19th rTMS session. Global cognition rose from 60.8 to 71.8, an 18.1% change in index score and a z-score improvement of 0.68. Memory rose from 37.2 to 45.4, a 22% change and a z-score improvement of 0.55. Verbal memory total accuracy rose from 25.0 to 54.0.
Across the remaining domains, executive functioning improved by 32.4%, working memory by 19%, and attention by 13.2%. Verbal functioning, her weakest domain at baseline, improved by 148%.
Who Benefits Most
The published rTMS evidence base sits with mild cognitive impairment and Alzheimer’s disease, using high-frequency stimulation of the left and/or right dorsolateral prefrontal cortex, and that is the population where standardized cognitive assessments have shown clear improvement. This report extends that question to early-onset disease in a single patient with laboratory confirmation.
Nothing here establishes which patients respond best. One case describes one patient.
Safety, Limits, and Caveats
The central limitation is the design. This is an uncontrolled single case with no sham condition and no blinding, so improvement on retesting cannot be separated from the natural course of the illness, from the effects of repeated exposure to the same test battery, or from the patient’s own expectations. The authors present it as a case report and frame its purpose as inspiring more clinical interest in exploring rTMS for dementia.
The strength of the report is the measurement. NeuroTrax is a validated, age- and education-normed instrument with high test-retest reliability, so the baseline severity and the direction of change are documented in index scores and z-scores rather than in impressions. Anything beyond hypothesis generation requires controlled studies.
Practical Takeaways
- Treat this as hypothesis-generating evidence, not a basis for offering rTMS as an Alzheimer’s treatment
- Confirm the diagnosis clinically and with laboratory workup before considering any neuromodulation, as was done in this case
- Screen for mood disorder with standard instruments, since depression can mimic cognitive decline and was formally excluded here
- Use a validated, age- and education-normed cognitive battery at baseline so any later change is measurable rather than impressionistic
- Record domain-level index scores and z-scores, not a single global number, because the domains in this report moved by very different amounts
- Point patients and families toward controlled trials of rTMS in mild cognitive impairment and Alzheimer’s disease
Related Studies and Research
Episode 31: Depression Explained, The Biology Behind the Darkness
Episode 32: Depression Recovery Roadmap: A Step-by-Step, Evidence-Based Plan
Default Mode Network Mechanisms of Transcranial Magnetic Stimulation in Depression
FAQs
Is early-onset Alzheimer’s disease different from late-onset?
Early-onset Alzheimer’s disease is a rare form defined by signs and symptoms appearing before age 65, while late-onset begins at or after 65. The patient in this report was 44.
When was the improvement measured?
Cognitive testing was repeated after the 19th rTMS session and compared against the patient’s baseline NeuroTrax scores.
How was the cognitive change actually measured?
With the NeuroTrax computerized platform, a validated instrument with high test-retest reliability that distinguishes cognitively healthy individuals from those with mild cognitive impairment. Scores are normed to age and education with a mean of 100 and a standard deviation of 15.
Can TMS replace Alzheimer’s medications?
No. This is a single case report. The reason alternatives such as neuromodulation are being investigated at all is that the efficacy of pharmacological treatment for both early and late-onset Alzheimer’s disease is significantly limited.
Bottom Line
A 44-year-old woman with definite early-onset Alzheimer’s disease improved on retesting after rTMS, with her global score rising 18.1%, memory 22%, executive functioning 32.4%, working memory 19%, attention 13.2%, and verbal functioning 148%. This is the first known case report of rTMS in a clinically and laboratory-confirmed early-onset patient. One uncontrolled case is a reason to study a treatment, not a reason to adopt it.
